Grantee: Alice Berger, Ph.D.
Named Award: Devereaux Outstanding Young Investigator
Position: Assistant Member
Institution: Fred Hutchinson Cancer Research Center, Seattle, WA
Project Title: Understanding The Etiology of Lung Cancer in Never-Smokers

Cancer Prevention Statement: To prevent cancer, we must understand the root causes. However, the causes of lung cancer (besides smoking) are not known. We will use DNA sequencing to determine whether environmental factors or underlying genetic factors contribute to the mutational processes in lung cancer in never-smokers.

General Audience Summary:
Lung cancer is the leading cause of cancer deaths in the United States. Cells from lung tumors contain abnormal DNA mutations that promote tumor growth. Sometimes, drugs can block the function of these mutations and improve patient survival. The mutations in lung tumors differ from person to person. Knowing the mutations in each tumor can help doctors know what therapy is best for each patient.

A major risk factor for lung cancer is smoking. However, people who have never smoked can also get lung cancer. This form of lung cancer is particularly common in women. Not very many tumors from non-smokers have been studied, so we don’t know all the mutations that occur in this type of lung cancer. As a result, we might be missing opportunities to match existing therapies to patients that will benefit. In this study, we want to identify the mutations in lung tumors from people who have never smoked. We think this information will help us propose the best therapies for this type of lung cancer and improve survival of lung cancer patients.

Mutations also provide a clue to the cancer’s origin. For example, cigarette smoke causes certain types of mutations. Finding these mutations in a lung tumor suggests that cigarette smoke might have contributed to the cancer development. We will look at the types of mutations present to determine whether second-hand cigarette smoke or other environmental exposures might have played a role in lung cancer development in people who have never-smoked.

Grantee: Andrea Branch, Ph.D.
Named Award: The Shure Family Charitable Foundation
Position: Professor
Institution: Icahn School of Medicine at Mount Sinai, New York, NY
Project Title: Reversing Drivers of Liver Cancer: Focus on Inflammation and Repair

Cancer Prevention Statement: Chronic liver disease creates fertile soil for the development of liver cancer, a highly deadly malignancy. This project will delineate the dysregulated cellular and molecular pathways in cirrhotic liver and pave the way for precision interventions to promote liver repair and prevent liver cancer.

General Audience Summary:
New interventions are urgently needed to prevent liver cancer. In the United States, liver cancer is increasing more rapidly than any other type of site-specific cancer. Complete removal/ablation of the tumor offers the only hope for cure, but patients receiving potentially curative therapy usually have a recurrence of the original tumor, or they develop a second tumor, underscoring the importance of primary and secondary liver cancer prevention. Hepatitis C virus (HCV) infection is a leading cause of liver cancer. Antiviral drugs allow most patients to be cured of HCV, however, if liver injury has already caused extensive scarring, patients continue to have a very high incidence of liver cancer, e.g., 2-4% annually. Liver cirrhosis (advanced scarring) is the most important liver cancer risk factor for patients with all types of chronic liver disease. Inflammation is a known cancer promoter and likely plays an important role in the development of liver cancer.

The goal of this project is to fill an important gap in what is known about the status of the liver in cirrhotic patients who have been cured of HCV with antiviral drugs. It leverages the large bank of liver specimens available at Mount Sinai and uses a powerful new technology pioneered by Mount Sinai’s Human Immune Monitoring Core (HIMC). The technique is called Multiplexed Immunohistochemical Staining on a Single Slide. This method will produce an unprecedented level of detail about the cells and molecular pathways leading to the persistent immune activation/inflammation and the abnormal capillaries/scar tissue that make the cirrhotic liver a fertile soil for liver cancer development. The project is expected to identify both dysregulated molecular pathways (that can potentially be blocked by targeted interventions) and liver repair pathways (that can be enhanced pharmaceutically). The findings may have an especially high impact because they are likely to apply across a broad range of liver diseases.

Grantee: Liang Liu, Ph.D.
Named Award: Awesome Games Done Quick
Position: Assistant Professor
Institution: University of Minnesota, Austin, MN
Project Title: A Novel UV Signature for Assessing Skin UV Damage and Cancer Risk

Cancer Prevention Statement: Skin cancer is the most common cancer with rising incidence in the United States. We have identified a unique biomarker panel for quantifying skin cancer risk information. We will further validate the clinical utility of this biomarker panel in risk stratifying patients for early cancer prevention.

General Audience Summary:
Skin cancer is the most common cancer in the United States, affecting more people than all other cancers combined. While skin cancer is largely preventable, its incidence continues to rise due to a low public compliance with skin cancer prevention and protection against ultraviolet (UV) exposure. This low compliance is largely attributable to the lack of objective risk information to educate and motivate susceptible individuals to avoid sunburn and minimize skin cancer risk. To address this unmet healthcare need, we propose to develop a reliable and objective test for risk stratifying individuals to enable early skin cancer prevention. To achieve this goal, we performed comprehensive genomics, bioinformatics and statistical analyses, which identified a novel biomarker panel specific to skin cancer. In this study, we will validate the utility and sensitivity of the biomarker panel as a skin cancer risk indicator. We will test the clinical applicability of the biomarker panel using a non-invasive technique to obtain skin biopsy from sun-exposed and non-exposed areas in sunburn patients. A custom-designed expression assay will be performed to simultaneously quantify the expression of the biomarker genes. Comparative expression analyses between sun-exposed skin and non-exposed skin will reveal whether the biomarker is present in sunburned skin. In addition, we will test the sensitivity and specificity of the biomarker in distinguishing premalignant skin or skin cancer tissue from non-malignant skin through rigorous experimental and statistical analyses. Successful demonstration of the utility of the biomarker panel will lead to the development of an affordable and non-invasive test to identify individuals at high risk of skin cancer who would benefit from education to encourage their avoiding sunburn and adopting behavior to prevent skin cancer.

Grantee: John McDonald, Ph.D.
Named Award: Michele and Drew Figdor Award
Position: Professor of Biology and Director, Integrated Cancer Research Center
Institution: Georgia Institute of Technology, Atlanta, GA
Project Title: Noninvasive Test for the Detection of Type I and Type II Ovarian Cancer

Cancer Prevention Statement: Using our previously established machine-learning approach to ovarian cancer diagnostics, we propose to establish a panel of serum metabolites that can non-invasively and accurately distinguish between low-grade and high-grade ovarian cancers.

General Audience Summary:
We recently demonstrated the exceptional accuracy (99-100%) of a novel approach to ovarian cancer diagnostics that combines state-of-the-art analytical chemistry methods with a branch of artificial intelligence called machine learning. In the proposed pilot study, we will evaluate the feasibility of developing a test that can accurately distinguish between ovarian cancers with low malignant potential (Type I) from those with high malignant potential (Type II) early in the progression of the disease. Such a test would not only revolutionize the manner in which ovarian cancer onset, development and recurrence is monitored, but additionally, may shed novel insight on the molecular interactions underlying high vs. low malignant disease thereby leading to potentially leading to more effective therapies.

Fellow: Heini Natri, Ph.D.
Named Award: Marcia and Frank Carlucci Charitable Foundation
Position: Postdoctoral Researcher
Institution: Arizona State University Foundation for a New American University, Tempe, AZ
Project Title: Sex-Specific Genetic Mechanisms Underlying Cancer Susceptibility

Cancer Prevention Statement: This study aims to understand the mechanisms of genetic predisposition to cancer. This work is necessary for understanding and predicting who is at increased risk of developing cancer, for early detection of cancer in those individuals, and for the development of better treatments for cancer.

General Audience Summary:
An individual with a genetic predisposition to cancer is at increased risk of developing cancer. Genetic predisposition results from specific genetic variants that are inherited from a parent. Inherited genetic variants play a major role in about 5-10% of all cancers. The mechanisms through which these variants affect cancer risk and progression are not well understood. Precision medicine is an approach that uses information of the patient’s genetic makeup to guide treatment decisions, monitor progression, and assess treatment outcomes. Such personalized approaches may result in higher treatment success and lower toxicity. However, because the molecular mechanisms of genetic cancer susceptibility are not well understood, it is still difficult to predict who will likely develop cancer, whose cancer will progress, and who will respond to treatments.

Many cancer types show a sex-bias in occurrence: in general, men are in a higher risk of developing cancer. Men and women differ in their genetic makeup, which, together with e.g. hormonal and lifestyle effects, may contribute to the sex-bias. Furthermore, the sexes differ in their response to some forms of chemotherapy and immunotherapy, indicating underlying differences in male and female tumors. These differences are likely partly due to the differences between X and Y chromosomes. However, sex differences are rarely considered in the development of cancer therapies.

The main goals of this study are 1) to understand the mechanisms through which inherited genetic variants contribute to cancer occurrence and progression, and 2) to investigate the sex-specific effects underlying sex-bias in cancer occurrence and progression. This work is crucial for understanding and predicting who has an increased risk of developing cancer, for early detection of cancer in those individuals, and for development of better, more targeted treatments for cancer.

Fellow: Cheng Peng, Sc.D.
Named Award: Awesome Games Done Quick
Position: Postdoctoral Research Fellow
Institution: Brigham and Women’s Hospital, Boston, MA
Project Title: Dietary Prevention of Breast Cancer Among High-Risk Individuals

Cancer Prevention Statement: Carotenoids represent a novel opportunity to prevent breast cancer in high risk women. Using genetic risk scores, mammographic density and metabolomics data, we aim to develop an actionable strategy to promote carotenoids intake, which may reduce breast cancer risk, and ultimately prevent cancer.

General Audience Summary:
Breast cancer is the leading malignant disease in women worldwide. Globally, an estimated 1.7 million new cases of breast cancer were diagnosed in 2012, and over 520,000 women die of the disease. Not every woman has an equal chance of developing breast cancer. Women with heritable genetic markers (called single nucleotide polymorphisms) or high mammographic density may have 2-20-fold higher risk of breast cancer compared to the general population. To date, many heredity genetic testing companies (such as Myriad Genetics) now release testing results to individual patients and their healthcare providers; and 34 states have required healthcare providers report to women with dense breasts. However, despite some of the invasive clinical options (e.g., mastectomy, oophorectomy and chemotherapy), after being identified as high-risk individuals, women usually receive limited advice on how to reduce their breast cancer risk. In this fellowship application, I propose an actionable targeted personal level dietary prevention strategy (carotenoids) to reduce breast cancer risk among women with high breast cancer risk profiles identified through heritable genetic testing and mammographic screening. I will further explore the underlying biology linking carotenoids intake and reduced breast cancer risk using pre-diagnostic metabolomics information. This work will help to integrate dietary recommendations into personalized breast cancer risk-reducing plans. Identifying individual level prevention strategies that could be integrated into daily life would be an actionable step forward to reduce breast cancer risk among high-risk individuals. Our proposed research is of great public health significance and motivates women at high risk to actively make lifestyle and behavior changes to decrease the likelihood of developing breast cancer.

Grantee: Kenneth Tercyak, Ph.D
Named Award: The Sanford Figdor Award in Melanoma Research
Position: Professor of Oncology & Pediatrics, Co-Leader of Cancer Prevention & Control Program
Institution: Georgetown University, Washington, D.C.
Project Title: A Mobile Text Messaging Intervention for Indoor Tanning Addiction

Cancer Prevention Statement: Melanoma is the leading cancer diagnosis among young woman in the United States.  Indoor tanning is one risk factor for melanoma that can be modified by incorporating healthy behavioral habits to prevent cancer before it starts. This project will test an interactive mobile text messaging program to help young women who are addicted to indoor tanning reduce their melanoma risk.

General Audience Summary:
Indoor tanning in young adult women is associated with early-onset melanoma. Studies show that about 25 percent of young women who indoor tan become addicted to indoor tanning in a way that is similar to drugs, alcohol and tobacco. Like other addictive substances, indoor tanning is marketed to young women in ways that appeal to unfounded health benefits and perceived benefits to physical appearance. These factors fuel the exposure to this melanoma risk among young women.  To date, few resources exist to alter this addictive behavior. This study will advance the science of melanoma prevention by integrating new intervention features to support behavior change and test the efficacy of a mobile text messaging program to quit indoor tanning.  This research not only has the potential to save young women’s lives, but also to break new territory in the field of behavioral prevention of melanoma.

Grantee:  Sigrid Carlsson, M.D.
Named Award: The Marvin Davis Estate Research Grant
Position: Assistant Attending Epidemiologist
Institution: Sloan Kettering Institute for Cancer Research, New York, NY
Project Title: Optimizing prostate cancer screening through the electronic health record

Cancer Prevention Statement:
Primary care physicians need guidance in talking to patients about “shared decision making” and “smarter” prostate cancer screening in a way that saves lives and avoids diagnosing slow-growing tumors. We will develop a computer system tool to help doctors facilitate discussions about the benefits/harms of prostate cancer screening.

General Audience Summary:
While national screening programs for major cancers, e.g. breast and colorectal cancer, have been embraced, screening for prostate cancer—the most common cancer in men and the third most common cause of cancer-related death among U.S. men—has remained controversial. This controversy is due to clear benefits of prostate specific-antigen (PSA) screening in preventing metastatic prostate cancer and cancer deaths, which is balanced by the clear harms of overdiagnosis and overtreatment, including the risk of serious side effects such as urinary leakage and sexual dysfunction. Ongoing efforts are focused on “smarter” ways to screen that focus on men who have the highest risk of aggressive prostate cancer, while minimizing harms of overdiagnosis and overtreatment.

As of 2017, multiple professional guideline groups, including the United States Preventive Services Task Force (USPSTF) and the American Urological Association, recommend “shared decision making” (discussing pros and cons) between men and their doctors for prostate cancer screening. The guidelines on prostate cancer screening are fairly complex and can be difficult for physicians to remember. Screening remains relatively underused in younger, healthy men, while it is overused in the older, less healthy population. Physicians need guidance on how to have conversations about shared decision making and how to apply smarter screening approaches. We hypothesize that the physicians’ electronic health record system is ideal to implement clinical decision-support tools around shared decision making for prostate cancer screening. 

Fellow: Varun Chandrashekaran, Ph.D.
Position: Postdoctoral Fellow
Institution: Joan & Sanford I. Weill Medical College of Cornell University, New York, NY
Application Title: Prevention of HNSCC by Using Receptor Selective Agonists

Cancer Prevention Statement:
We need better preventive approaches for head and neck cancers. We’ve shown that one type of retinoid (vitamin A derivative) drug can prevent tumor formation in a mouse model of this cancer. We propose that a combination of retinoids will have greater cancer preventive effect.

General Audience Summary:
Head and Neck Squamous Cell Carcinoma (HNSCC) is the seventh most common cancer worldwide. Surgery is the preferred treatment for early stage HNSCC. However, aggressive local invasion and metastasis lead to a high recurrence rate, which makes HNSCC a challenging disease to treat. To this end, prevention of HNSCC is an important goal.

Retinoids include vitamin A and related molecules. 13-Cis-RA, a retinoid, can reverse premalignant lesions and prevent the development of second primary tumors in head and neck cancers because of its ability to restore normal cell growth and differentiation. Our lab uses a carcinogen to induce HNSCC tumors in mice, and has shown that the synthetic retinoid CD1530 effectively prevents the development of oral tumors in the mice.

AC261066 is another synthetic retinoid drug that has been identified in our laboratory. AC261066 may also have cancer preventive effects in HNSCC because its target protein is a purported tumor suppressor. My hypothesis is that AC261066, in combination with CD1530, will prevent the induced HNSCC tumor formation with greater efficacy than either drug alone.

Collectively, this research has the potential to identify new strategies for more effective retinoid-based cancer prevention in HNSCC. These findings should save lives by preventing cancer in high-risk individuals. 

Fellow: Sho Kitamoto, Ph.D.
Named Award: The Marvin Davis Estate Research Grant
Position: Postdoctoral Fellow
Institution: The Regents of the University of Michigan, Ann Arbor, MI
Project Title: The role of oral pathobionts in the development of colon cancer

Cancer Prevention Statement:
This proposal will clarify whether genotoxic bacteria residing in the oral cavity promote colon cancer development. If successful, the detection/clearance of genotoxic bacteria in the mouth could be useful for the early detection and prevention of colon cancer.

General Audience Summary:
Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the United States. Recent studies show that not only genetic factors (e.g., family history), but also environmental factors (e.g., aging, western diet) contribute to colorectal cancer risk.

Gut bacteria have attracted considerable attention as potential environmental risks. For example, a certain type of gut bacteria, which cause DNA damages in the colonic cells, accumulate in cancer tissues. Since DNA damage is a known risk for cancer, an abnormal expansion of these bacteria may lead to colorectal cancer.. However, we still do not know how these DNA-damaging bacteria expand in the colon.

We found that DNA-damaging bacteria accumulate in the mouth as a result of periodontal disease in mice. Expanded “bad” oral bacteria can reach the colon via a natural orogastric translocation. Therefore, the presence of periodontitis significantly increased the risk for colorectal cancer in mice. The evidence that periodontal disease is a significant risk for colorectal cancer in humans supports these results.

In this study, we will further characterize the bad oral bacteria and unravel the mechanism by which these bacteria cause colorectal cancer. It is expected that the early detection of genotoxic bacteria in the mouth can be utilized as a non-invasive method for identifying individuals at increased risk for colorectal cancer, and that optimal oral hygiene can reduce the risk of colorectal cancer

Grantee: David Montrose, Ph.D.
Named Award: Prevent Cancer Foundation Board of Directors Research Fund
Position: Assistant Professor
Institution: Stony Brook University School of Medicine
Project Title: Modulating the microbiota and metabolome for GI cancer prevention

Cancer Prevention Statement:
We will investigate whether changing the types of bacteria or the small molecules they produce can prevent the formation of pre-cancerous polyps in the intestine by affecting stem cell function. These studies have the potential to lead to novel approaches for colon cancer prevention.

General Audience Summary:
Colon cancer is the second leading cause of cancer-related deaths in the U.S. and develops as a result of the change from normal colon tissue to pre-cancerous tissue to cancer. This transition typically takes 10 to 15 years, which provides time to prevent cancer development. Currently, colonoscopies are the best way to prevent colon cancer by removing pre-cancerous tissue. Although this procedure is helpful, it is less than perfect, and some people avoid it because of its invasiveness. Medications can also prevent cancer development by disrupting the cellular pathways that support the progression from normal tissue to cancer. However, side effects can limit their use.

Given the limitations of current options to prevent colon cancer, it is clear that alternative methods are needed. The colon contains trillions of bacteria, which can impact cancer development. We believe they do this by releasing small molecules into the colon, which interact with the body’s cells to disrupt their molecular pathways. Our group published a research study showing that changing the types of bacteria in the colon and the small molecules they produce was associated with lower amounts of pre-cancerous tissue and reduced function of colon stem cells. Since stem cells are thought to contribute to colon cancer development, we believe all of these changes are related and by changing the types of bacteria and the small molecules they produce, we can reduce the risk of developing colon cancer.

Our work is the first to demonstrate an association between changes in bacteria and stem cell function. We will directly test whether altering bacteria and the molecules they produce can, in fact, affect stem cell function and ultimately reduce cancer risk. This has the potential to open an entirely new approach for colon cancer prevention.

Grantee: Christopher J. Recklitis, Ph.D. 
Named Award: Awesome Games Done Quick Research Grants
Position: Senior Psychologist
Institution: Dana-Farber Cancer Institute, Boston, MA
Project Title: SunSmart: Preventing Secondary Skin Cancer in Young Adult Cancer Survivors

Cancer Prevention Statement:
Young adult cancer survivors (YACS) have an elevated skin cancer risk, but do not practice sun protection (SP)  to reduce this risk. By testing SunSmart, a sun protection education intervention targeting young adult cancer survivors, this study can prevent future skin cancers in this high-risk population.

General Audience Summary:
After completing cancer therapy, young adult cancer survivors (YACS) are at very high risk for being diagnosed with a second cancer, and more than half of these second cancers will be skin cancers. To reduce their skin cancer risk, young adult cancer survivors are counseled to limit their exposure to ultraviolet (UV) light, but studies show most do not practice adequate sun protection. Despite their skin cancer risk and poor sun protection, there are currently no evidence-based interventions to prevent secondary skin cancers in young adult cancer survivors.

To respond to their unique needs, we propose to refine and test SunSmart, a new sun protection video intervention designed to prevent secondary skin cancer in young adult cancer survivors by increasing their adherence to recommended sun protection. Prior research has shown that educational interventions to increase sun protection in healthy young adults are most effective when they include messages emphasizing negative effects of UV exposure on appearance, but this has not been studied in young adult cancer survivors.

SunSmart is an engaging video intervention that is specifically tailored to young adult cancer survivors, and can be delivered on the internet. In Phase 1 of this study, we will use feedback from young adult cancer survivors to refine the SunSmart educational videos before they are pre-tested as a web-based intervention. In Phase 2, we will determine how effective the SunSmart interventions are in changing young adult cancer survivors’ sun protection attitudes and behaviors. Developing a new intervention to increase young adult cancer survivors’ sun protection behaviors will prevent future skin cancers in this vulnerable population.

Fellow: Qinggong Tang, Ph.D. 
Named Award: Awesome Games Done Quick Research Grants
Position: Assistant Professor 
Institution: University of Oklahoma, Norman, OK
Project Title: Early Cancer Detection by Multi-modal Endoscopic Optical System

Cancer Prevention Statement:
Colorectal cancer is the third most common form of cancer diagnosed in both men and women in the United States. We propose to develop an endoscopic multi-modality optical imaging system for early colon cancer detection, which can improve the survival rate of the patients.

General Audience Summary:
Colorectal cancer is a cancer that starts in the colon or the rectum. These cancers can also be named colon cancer or rectal cancer, depending on where they start. Colorectal cancer is the third most common form of cancer diagnosed in both men and women in the United States.  It is the third leading cause of cancer-related deaths in women in the United States and the second leading cause in men.

When colorectal cancer is found at an early stage before it has spread, it has a five-year survival rate of 90 percent, but the survival rate drops to less than 10 percent after metastasis. Unfortunately, only 25 percent of colorectal cancer cases are discovered in the early stage. Excisional biopsy and histology is currently the gold standard for cancer diagnosis, but there are high false negative rates due to sampling errors. Using current video colonoscopy to guide the biopsy can only provide data on superficial tissue structure and does not have the depth-resolved capability to image the colonic mucosa and submucosa, where early-stage colon cancer arises. New high-resolution imaging techniques tools could minimize the invasiveness of screening, aid early colorectal cancer detection and guide biopsy procedures to improve the sampling accuracy. The objective of this application is to develop an endoscopic multi-modality optical imaging system for early cancer detection.

Fellow: Trang VoPham, Ph.D.
Named Award: The Richard C. Devereaux Fellowship
Position: Postdoctoral Research Fellow
Institution: Fred Hutchinson Cancer Research Center, Seattle, WA
Project Title: Reducing PM2.5 exposure and lung cancer risk using spatial data science

Cancer Prevention Statement:
Fine particulate matter air pollution (PM2.5) is a known lung cancer risk factor. Using spatial data science, we will develop a PM2.5 forecasting system and propose an educational and behavioral intervention to reduce personal PM2.5 exposure, reduce lung cancer risk, and ultimately prevent cancer.

General Audience Summary:
Lung cancer is the most commonly occurring and deadliest cancer worldwide. The International Agency for Research on Cancer announced in 2013 that there is strong evidence showing that exposure to fine particulate matter air pollution called PM2.5 increases the likelihood of developing lung cancer, even among those who have never smoked cigarettes. In fact, 15 percent of all lung cancer deaths are attributed to PM2.5 exposure.

PM2.5, which includes tiny particles too small for the eye to see, comes from man-made sources, such as cars, and is found all around us. People breathe in PM2.5 particles that penetrate deep into lungs, and 13.6 percent of Americans live in areas where PM2.5 levels exceed national public health standards.

We will develop a behavioral and educational intervention to promote healthy behaviors, such as avoiding high-traffic areas, to reduce personal exposure to PM2.5 and thus reduce lung cancer risk. We will use the latest advances in spatial data science, deep learning and big data to create a system to forecast real-time PM2.5 exposure with high accuracy and precision, just like weather forecasts. These PM2.5 forecasts will be a vast improvement over current air quality predictions. We expect that including these forecasts in an intervention will change people’s beliefs, knowledge and behaviors around PM2.5 exposure and lung cancer risk. This will be the first intervention study in the U.S. aimed at reducing PM2.5 exposure and cancer risk. Ultimately, since environmental exposure to PM2.5 can be reduced by adopting healthy preventive behaviors, this study can provide useful information on how to modify PM2.5 exposure to decrease the likelihood of developing lung cancer.

Leah Frerichs, Ph.D.

Named Award: Marvin Davis Estate
Applicant Title: Assistant Professor
Institution: The University of North Carolina at Chapel Hill, Chapel Hill, NC
Project Title: A randomized trial of an American Indian colon cancer screening strategy

American Indians are the only US racial or ethnic group who have not had decreases in colorectal cancer cases and deaths. This research project will test a culturally-sensitive multimedia video designed to overcome literacy and cultural barriers to improve colorectal cancer screening among American Indians.

General Audience Summary:

Despite effective prevention and screening tests, colorectal cancer is one of the most common types of cancer and a leading cancer killer. Largely due to increases in colorectal cancer screening over the past two decades, the number of individuals who are diagnosed and die from colorectal cancer has been substantially reduced. Yet, these improvements have not been equitably distributed across all racial and ethnic groups. American Indians, in particular, are the only racial and ethnic group who have not observed significant decreases in diagnoses and deaths from colorectal cancer and have persistently low use of screening tests. A critical barrier to improving the use of colorectal cancer screening among American Indians is overcoming health literacy, social, and cultural barriers to understanding and communicating with healthcare providers about screening options. Multimedia videos, called decision aids, can help patients understand complicated health information and encourage more effective communication with healthcare providers. These tools have been shown to improve use of colorectal cancer screening in medically underserved and vulnerable populations. Dr. Frerichs and her team designed and produced a colorectal cancer screening decision aid specifically for American Indian populations that uses content and messengers who are sensitive to relevant socio-cultural barriers (e.g., spiritual advisors who are credible to American Indians endorse screening). In this proposal, the research teams aims to rigorously evaluate their culturally-adapted decision aid with American Indians (n=120) ages 50 to 75 who are not up-to-date with colorectal cancer screening. This research team will assess the decision aid’s impact on colorectal cancer-related knowledge, attitudes, communication, and screening behaviors. Their project will lead to new insights about culturally-appropriate communication about cancer screening and has the potential to improve colorectal cancer screening among a population with persistent health disparities.

Jo Freudenheim, Ph.D.

Named Award: Richard C.  Devereaux Grant
Applicant Title: Professor and Interim Chair
Institution: The Research Foundation for The SUNY on behalf of University at Buffalo, Buffalo, NY
Project Title: Effects of Electronic Cigarette Use on the Human Lung

Smoking greatly increases lung cancer risk. Electronic cigarettes (e-cigs) are increasingly being used for smoking cessation and by people who have never smoked. Biological effects of e-cigs are not known. This study will compare lung tissue from healthy young adults, smokers, never smokers and e-cig users.

General Audience Summary:

Lung cancer is a leading cause of cancer, accounting for more than 1.8 million new cases and close to 1.6 million deaths worldwide annually. Smokers have 20 times greater risk of lung cancer. Electronic cigarettes (e-cigs) have come into the market place, widely used by smokers in an attempt to quit or to skirt indoor smoking bans. E-cigs are increasingly being used both by young adult non-smokers and instead of cigarettes among smokers; use of e-cigs is now more common than the use of cigarettes among youth. E-cig sales total more than $1.7 billion per year. While likely less toxic than cigarettes, because they do not burn tobacco, it is not known if these products are safe, or what the potential is for harm. Users inhale a variety of e-cig liquid constituents and their break down products, many of which are irritants and provoke inflammation. The potential for these exposures to contribute to lung cancer or other diseases needs to be determined in humans; a way to do this is to detect lung toxicity in humans. This research team currently has a study underway to examine brushings of lung tissue obtained by bronchoscopy, a procedure where the lung is accessed with a thin scope in a patient under local anesthesia and light sedation. The study includes never smokers, smokers and e-cig users, all adults aged 21-30. In that study, they will examine a number of important biomarkers related to inflammation and to cancer. For the proposed study, they will add an examination of DNA methylation of cells in the lung tissues. Altered DNA methylation is known to be important in the development of lung cancer and it is known that there are changes in DNA methylation with smoking. It is not known if e-cigs affect DNA methylation. The comparison of lung tissues from never smokers, smokers and e-cig users will provide critical information regarding toxicity of e-cigs for humans including DNA methylation changes.

Rosa Munoz Xicola, Ph.D.

Named Award: Figdor Family Grant
Applicant Title: Associate Research Scientist
Institution: Yale University School of Medicine, New Haven, CT
Project Title: New DNA repair alterations in hereditary cancer development

Patients with undefined cancer disorders that seem to be inherited tend to have a very high risk of developing cancer at young ages. Identifying their molecular cause will allow us to tailor health care measures to prevent new diagnosis and provide adequate treatment to patients and family members.

General Audience Summary:
Lynch syndrome is an inherited cancer disorder caused by genetic alterations in the Mismatch Repair (MMR) genes, which repair the DNA. Over half of presumed Lynch cases do not have genetic alterations in the MMR genes and these are referred to as Lynch-Like Syndrome (LLS). LLS patients are treated as LS patients and go through strict, aggressive cancer supervision measures. In their preliminary studies, LLS patients showed a significant enrichment of genetic variants in other DNA repair genes in comparison to people without cancer. Furthermore, these LLS patients are younger than colorectal cancer (CRC) patients without an inherited disorder and have an average of 2.2 first-degree relatives with cancer, including breast. The research team hypothesizes that there is a sizable group of CRC patients with a genetically predisposing cancer condition due to genetic variants in DNA repair genes that promote genomic alterations and consequently cancer development. This likely explains a number of the familial occurrences of multiple different cancers, such as breast and CRC. The goal of this proposal is to determine the extent to which genetic variants in DNA repair genes contribute to cancer development in patients with a strong family history of CRC or breast cancer. This proposal has the potential to have a significant impact. Establishing the genetic cause of undefined cancer disorders could allow us to tailor cancer prevention and treatment, ultimately reducing cancer deaths. Moreover, this proposal might identify the missing link to explain familial cases with the most common cancers, CRC and breast.

Rajesh Panigrahi, Ph.D.

Named Award: Figdor Family Fellowship
Applicant Title: Postdoctoral Research Associate
Institution: University of Massachusetts Medical School, Worcester, MA
Project Title: A virus-like particle vaccine for prevention of Epstein-Barr virus (EBV) associated cancer

Despite enormous success of virus-like particle (VLP) vaccines that safely prevent Hepatitis B virus (HBV) and Human papillomavirus (HPV) associated cancers, no EBV vaccine is licensed. EBV, a major human tumor virus cannot form VLP vaccines. Using a novel fusion platform, the research team developed an EBV-VLP candidate for cancer prevention and aim to develop an EBV vaccine that safely stimulates protective immunity, to eliminate infection and cancer.

General Audience Summary:

Epstein-Barr virus (EBV), a strictly human virus, is present in multiple cancers (B some T-cell lymphomas, Leiomyosarcomas, nasopharyngeal and some gastric carcinomas, others). While global improvement in screening and vaccination has led to dramatic declines in cancer caused by other tumor viruses, the incidence of EBV+ tumors have grown coordinate with development. This is attributed to increasing age of primary infection, a risk factor for “mono” and in turn EBV+ Hodgkin lymphoma, as well as to survival of persons most vulnerable to EBV+ cancers (transplant recipients, elderly, malaria or HIV-infected, residents of SE Asia and N Africa). Diverse treatment strategies cause long-term complications and overall mortality remains high. To eliminate infection and cancer, their goal is to develop an EBV vaccine that safely stimulates protective immunity. Though weakened viruses often make superior vaccines, tumor viruses are considered dangerous. The protein gp350/220 is required for EBV to attach to cells and initiate infection. Though antibodies to gp350 potently block infection in test systems, it was minimally effective when used alone in vaccine trials. Single proteins often fail to elicit strong immunity, whereas virus-like particles (VLPs) form repeated protein units that do (Hepatitis B, HPV VLP vaccines). As EBV cannot form VLPs, the research team has engineered a novel VLP fusing gp350/220 to an avian viral protein that does. In standard mice, EBV-VLPs were safe and stimulated strong antibody-based protection. But, T-cell immunity, the key to prevention of EBV-disease cannot be authentically studied nor disease prevention proved in standard mice. Exciting new models of mice transplanted with human immune cells have revealed how T-cells control EBV. They propose to generate, compare and test the effectiveness of 4 optimized EBV-VLPs in state-of-the-art humanized mice, providing the critical knowledge required to initiate clinical trials of this promising vaccine candidate.

Matthew Stachler, M.D., Ph.D.

Named Award: Marcia and Frank Carlucci Charitable Foundation Grant
Applicant Title: Associate pathologist
Institution: Brigham and Women’s Hospital, Inc.
Boston, MA
Project Title: Genomic features associated with cancer development in Barrett’s biopsies

Despite a known precursor and screening, most esophageal cancers are not detected early and are incurable. This research team aims to determine the genomic differences in the precursor between people who do and do not get cancer, in order to develop markers of disease progression for early detection and treatment.

General Audience Summary:

Barrett’s esophagus is a change in cell type that lines the esophagus and is due to heartburn or reflux. Over time it can progress and develop into esophageal cancer. Since millions of Americans harbor Barrett’s esophagus but only a minority will get cancer, treating everyone with Barrett’s is not feasible (nor advisable due to side effects). It is suggested to undergo repeated upper endoscopic screening with multiple biopsies of the Barrett’s to look for signs of progression. Unfortunately, the majority of people are not detected early and present with incurable disease. Better strategies are needed to determine which patients with Barrett’s are at high risk of getting cancer in order for more intensive screening or early therapy so that the disease can be treated when it is easily curable. Dr. Stachler’s previous work has looked at the genomic alterations (changes in the DNA) found in Barrett’s tissue within patients with esophageal cancer. These studies have found key alterations in the Barrett’s DNA before any other signs of progression and have changed the way we think Barrett’s esophagus progresses into cancer. This raises the exciting possibility to use these genomic alterations as a marker to identify who is at risk of progression. The studies proposed in this grant will take the next step in this process by looking to identify these alterations (and discover new alterations) in a collection of clinical biopsies from both patients that progressed to cancer and patients who have had benign Barrett’s esophagus and never got cancer. Specifically, this research team proposes to use routine clinical biopsies prepared in the same manner done for clinical care with cutting edge technologies (next generation sequencing of Formalin-fixed, Paraffin-embedded (FFPE) tissue using a small, custom designed targeted gene panel) and computational approaches that can be translated into clinical testing. These studies will be the building blocks for larger studies aimed at testing and validating these markers.

Walter R. Thompson, Ph.D.

Applicant Title: Regents’ Professor & Associate Dean
Institution: Georgia State University Research Foundation, Inc., Atlanta, GA
Project Title: The Little Cigar and Cigarillo Photovoice Feasibility Project

Little cigar and cigarillo (LCC) smoking has increased, particularly among African-American youth. Cigar use increases the risk of developing cancer. This research team’s research will assess factors that can prevent the initiation of LCC smoking.

General Audience Summary:

Little cigars and cigarillos (LCCs) are combustible tobacco products that are inhaled like cigarettes and are similar in size, shape, filtering, and tobacco pH. The health risks associated with smoking LCCs are very similar to those from cigarettes: they cause nicotine dependence and several forms of cancer. LCCs are growing at an alarming rate among youth, especially among African-Americans; a group who suffers and dies disproportionately from tobacco-caused cancers. Continued use of LCCs may increase the risk of cancer-related health disparities among African-Americans. In a landmark decision, in May 2016, the Food and Drug Administration (FDA) decided to regulate LCCs, along with other tobacco products. Although LCCs are under the FDA’s regulatory authority, they are still less regulated than cigarettes. Unlike cigarettes, LCCs are available in characterizing flavors (e.g. vanilla, grape, etc.); have fewer product advertising and marketing restrictions; and have no minimum pack size requirements. The research team’s preliminary data suggests that these less-regulated features are appealing to young adult LCC users and influences their perception of risk of LCCs. While their preliminary data on young adults are informative, they are ineffective for explaining how LCC advertising influences susceptibility and the decision to smoke LCCs among adolescents. The objectives of this study are to examine the association among environmental factors (i.e. LCC advertisements) and susceptibility/intention to use LCCs and to use this evidence to inform the development of youth-centered advocacy campaigns that bring awareness to the consequences of LCC use and environmental factors that promote its use.

Zhenyu Zhong, Ph.D.

Named Award: Prevent Cancer Foundation Board of Directors Research Fund
Applicant Title: Assistant Professor
Institution: University of Texas Southwestern Medical Center
Project Title: Prevention of Obesity-induced HCC by Inhibition of Sterile Inflammation

Obesity promotes the development of liver cancer, however, the underlying mechanism remains elusive. This proposal will investigate how obesity induces liver inflammation and cancer development, and will promote the development of new preventive strategies for obesity-associated liver cancer.

General Audience Summary:

Obesity is a major health problem in the United States and it can promote the development of liver cancer. However, how obesity induces liver cancer remains largely unknown. Dr. Zhong and his research team’s previous work suggests that obesity-induced liver inflammation is the key switch that drives the progression of mild fatty liver disease to hepatocellular carcinoma, a dominant form of liver cancer. This research proposal aims to identify previously unknown key player(s) that control obesity-induced inflammation and liver cancer development, thereby fostering the design of new preventive therapies for this devastating disease. Dr. Zhong recently identified two counteracting players that control the extent of obesity-induced liver inflammation, therefore he hypothesizes that the interplay between these two players in the context of obesity determines whether liver cancer would develop. Dr. Zhong will test his hypothesis using a new animal model of human liver cancer, which was recently developed in their laboratory. He is confident that the completion of the current proposal will provide a much-needed mechanistic insight of how obesity promotes liver cancer development, and will therefore enable the development of new preventive strategies for obesity-associated liver cancer in patients.

2017 Special Award

Brian Rood, M.D.

Named Award: Sarah Howard Childhood Cancer Fund for Our Children’s Health Grant
Applicant Title: Director of Clinical Neuro-Oncology
Institution: Children’s Research Institute, Washington, D.C.
Project Title: Medulloblastoma Risk and the Germline Foundation of Predisposition

Microsatellites are DNA markers that associate non-randomly with disease states and can influence the function of nearby genes. The identification of medulloblastoma-specific microsatellite genotypes will provide the ability to predict the relative risk of individuals and yield insight into potential preventative strategies.

General Audience Summary:

Medulloblastoma is the most common type of pediatric malignant primary brain tumor. The early age of peak incidence indicates an accelerated tumor initiation process, suggesting that a favorable genetic environment for tumor formation may exist in those individuals who are eventually diagnosed. Microsatellites are small runs of repeated DNA code/letters in DNA sequences. The number of repeats varies somewhat between different individuals and also between the two copies of DNA in each individual. As a result of their variable nature, microsatellites can be used to identify individuals and populations from their DNA. In addition, microsatellites are sources of DNA instability, where an alteration in the number of the repeated sequence is associated with many different diseases including cancers. These alterations are hypothesized to lead to changes in cell biology through various mechanisms. Thus, changes in microsatellite sequences contribute to biological differences that can contribute to cancer development. Dr. Rood and his team hypothesize that medulloblastoma formation is correlated with microsatellite variations at specific regions in the DNA close to genes. In fact, a small pilot analysis of medulloblastoma patient germline DNA (from the body, not from the tumor), identified variations in 15 microsatellites regions that are significantly associated with the presence of the tumor compared to DNA from healthy individuals. Therefore, these cancer associated microsatellites existed before the tumor was formed and thus could mark a predisposition to cancer. The identification of those microsatellites could be a great tool to identify a population for early medulloblastoma detection. In addition, understanding the mechanism of the predisposition could improve understanding of how and why these tumors form in certain individuals and point the way toward preventative strategies.

Reginald Y. Gohh, M.D.

Applicant Title: Medical Director, Division of Organ Transplantation
Institution: Rhode Island Hospital, Providence, RI
Project Title: Nicotinamide for AK prevention in kidney transplant recipients

Findings from this study will further clarify the therapeutic potential of nicotinamide as a safe, inexpensive chemo-preventive in kidney transplant recipients at high risk for non-melanoma skin cancer.

General Audience Summary:
“Non-melanoma” skin cancers and pre-cancerous growths (actinic keratosis or “AKs”) develop at high rates in kidney transplant patients. When they do develop in these patients, they tend to be aggressive and require frequent medical procedures, often surgery, for their removal. If not removed, the pre-cancers can develop into skin cancers, and the skin cancers may spread and even cause death. It would be an important medical advance to reduce the occurrence and complications of these skin cancers and pre-cancers in kidney transplant patients with a safe, effective, well-tolerated treatment taken by mouth. Dr. Bostom and his team are testing oral nicotinamide (NAM)—a B-vitamin compound—to see if NAM treatment reduces the numbers of pre-cancerous growths and “non-melanoma” skin cancers in these patients.

Katherine Cook, Ph.D.

Named Award: The Living in Pink/Prevent Cancer Partnership Award
Institution: Wake Forest University Health Sciences, Winston Salem, NC
Project Title: Prevention of obesity-induced breast cancer and tamoxifen drug resistance

This study hopes to identify the impact of dietary fatty acid composition on obesity-induced breast cancer development. This may lead to women making more-informed food choices as a way to prevent breast cancer.

General Audience Summary:
Breast cancer is the most frequently diagnosed cancer in women: about 232,000 new cases are diagnosed each year. Obesity also is an epidemic in the U.S., as over 60% of women are overweight or obese. Several studies have shown a strong link between obesity and a greater risk of developing breast cancer. It is estimated that 3 out of 10 breast cancers may have been prevented if the women were not overweight.

The most common type of breast cancer expresses the estrogen receptor, and endocrine-targeted therapies are often used to treat them. Results from the breast international group (BIG) I-98 study indicate that obese women treated with tamoxifen had a poorer overall survival when compared to healthy weight women, suggesting a causal link between obesity and resistance to endocrine therapy.

Dr. Cook’s preliminary data show that, compared to lean mice, obese mice are more likely to develop breast cancer and to have a worse response rate to endocrine-targeted therapies.

Molecular signaling pathways such as the unfolded protein response (UPR) pathway and autophagy are identified as contributors to breast tumor development and cancer therapy resistance. Dr. Cook hypothesizes that elevated UPR and autophagy induction in mammary glands of obese mice promote tumor formation and impair responsiveness to anti-estrogen therapy. Targeting these pathways may prevent obesity-mediated primary breast cancer and prevent secondary breast cancer reoccurrence, thus reducing overall breast cancer mortality.

Nicole M. King, Ph.D.

Institution: Wayne State University, Detroit, MI
Project Title: Novel biomarkers for early detection of ovarian cancer

This study has the potential to provide early detection of ovarian cancer through screening with specific and sensitive biomarkers, ultimately changing detection and treatment of ovarian cancer in the future. 

General Audience Summary:
Ovarian cancer is responsible for the greatest number of deaths from gynecologic cancers and for the fifth greatest number of deaths from all cancers in American women. Currently, there is no effective screening test for ovarian cancer. Development of specific and sensitive biomarkers for ovarian cancer remains a challenge. A recent novel finding by Dr. King’s lab has shown that an inflammatory protein, myeloperoxidase (MPO), is present in ovarian cancer cells and tissues and is not present in normal ovarian tissues, thus suggesting an important role for MPO in this disease. The presence of MPO seems to be specific to ovarian cancer as minimal or no presence was detected in several other types of cancer. Her lab has also reported that MPO serves as a source of free iron, which may contribute to the development of ovarian cancer.

A preliminary study using a small number of patients in Dr. King’s lab has also shown that a combination of serum MPO and free iron levels can differentiate between early (stage I) ovarian cancer and healthy controls and between early- and late-state  ovarian cancer. Dr. King and her team will further test whether serum MPO and free iron can serve as biomarkers for early detection of ovarian cancer alone or in combination with commercially available tests for ovarian cancer. The outcome of this project is significant, because the development of a sensitive and specific method for early detection is widely recognized as a high priority to improve the diagnosis and treatment of this deadly disease. The proposed work is innovative, because, if it is successful, very specific, easily measured and relatively inexpensive mechanistically linked serum biomarkers would be available for the first time to detect ovarian cancer early.

Brittany Lasseigne, Ph.D.

Named Award: William J. Maier III Fellowship in Cancer Prevention
Institution: HudsonAlpha Institute for Biotechnology, Huntsville, AL
Project Title: Development of an Early Diagnostic Urine Test for Kidney Cancer

Kidney-cancer patient outcomes are dramatically improved with early diagnosis, so we are developing a urine DNA biomarker test for early detection and prevention of kidney cancer.

General Audience Summary:
Kidney cancer is the ninth most commonly diagnosed cancer in the U.S. In 2015, about 61,560 cases will be diagnosed, and 14,080 patients will die of the disease. When tumors are confined to the kidney, they can be surgically removed, and five-year survival rates are high. However, early symptoms are rare, later symptoms are not easily recognizable, and there are no clinical biomarkers for early detection. Once the cancer has spread outside the kidney, kidney cancer becomes harder to treat and much deadlier, showing the importance of early detection when tumors are still small and inside the kidney.

Dr. Lasseigne has identified differences in DNA between kidney tumor and normal tissue that can easily distinguish them, even in early-stage patients. These tissue biomarkers are strong candidates for development of a clinical diagnostic test for early kidney cancer. Urine is an optimal biofluid for detection of these biomarkers, because urine is produced in the kidney, and urine collection is non-invasive. About 50% of all DNA found in urine originates from the kidney, so Dr. Lasseigne and her team expect great success in detecting their biomarkers in urine samples. Their preliminary data suggest detection of these biomarkers is possible in patient urine, which provides an avenue for the development of a DNA-based diagnostic, non-invasive test for the early detection of kidney cancer. Dr. Lasseigne proposes to design, test and optimize a diagnostic test for kidney cancer. Successful implementation would aid in the early detection and prevention of kidney cancer, greatly improving patient care and outcomes.

Ranjan Preet, Ph.D.

Named Award: Lilly USA Research Award in Cancer Prevention and Early Detection
Institution: University of Kansas Medical Center Research Institute, Inc., Kansas City, KS
Project Title: The RNA binding protein HuR as a novel exosome biomarker in colon cancer

Colorectal cancer prevention is limited by lack of blood-based biomarkers, and this research aims to determine if a protein specifically secreted by colon cancer tumors can fill this void by providing a non-invasive approach for detecting colorectal cancer early.

General Audience Summary:
In 2016, it is estimated that over 134,000 Americans will be diagnosed with colorectal cancer. A major factor contributing to colorectal tumor progression is overexpression of oncogenes, inflammatory mediators and angiogenic growth factors. Exosomes are small secreted vesicles that contain biological materials such as RNA and proteins that can deliver this cargo to target cells. Tumor cells secrete higher amounts of exosomes that contain oncogenic cargo, and colorectal cancer patients have higher levels of circulating blood exosomes. This allows for their potential use as a disease marker. The goals of this study are to characterize a novel protein present in colorectal cancer exosomes and to determine if it can serve as a non-invasive biomarker for colon cancer screening. The study will characterize a novel protein that is selectively secreted from colorectal cancer cells, and Dr. Preet aims to explore this as a potential biomarker for development of a non-invasive blood-based detection method for colorectal cancer.

Victoria Seewaldt, M.D.

Named Award: The Green Flash Brewing Company Grant in Cancer Prevention and Early Detection
Applicant Title: Professor and Chair
Institution: Beckman Research Institute of the City of Hope
Project Title: Early Detection of Triple-Negative Breast Cancer

This research explores biological cues which may help detect triple-negative breast cancer earlier than through use of biopsy alone.

General Audience Summary:
Everyone knows a woman who had a normal mammogram or biopsy.  Yet despite these “normal” tests she went on to develop an aggressive cancer. When this happens in my clinic, I feel that I have betrayed my patient.

Part of the problem is that we know very little about how aggressive breast cancers develop. The majority of breast biopsies are evaluated by appearance (morphology) and not by biology; however, our studies provide evidence that biology can sometimes be even more important than morphology. In this study we aim to test whether some breast biopsies may look normal but have activation aggressive biology that, if left unchecked, promotes rapid progression to triple-negative breast cancers (TNBC).

Discovery of the BRCA1 gene has helped identify some women who are at highest risk of developing TNBC. However, many TNBCs occur in women without an inherited BRCA1, and a majority of these cancers (61-76%) have defective BRCA1 protein (BRCA1 protein is not in the nucleus). In our bench studies, we identified a signaling network (Wnt10B/HMGA2/EZH2) that blocks the ability of BRCA1 protein to get into the nucleus.

We tested whether the signaling network could identify women who, despite a normal biopsy, went on to develop TNBC. We tested biopsies from high-risk women in my clinic who had breast biopsies that were read as “normal” by the pathologist and subsequently did—or did not—develop TNBC within 12 months of biopsy. In preliminary data we observed that expression of our signaling network predicted 1) loss of working BRCA1 (loss of nuclear BRCA1) and 2) progression to TNBC within 12 months.

Our hypothesis is that activation of this network signaling predicts loss of nuclear expression of BRCA1 (loss of function) and can be used to improve early detection of TNBC.

2016 Special Awards

Dorraya El-Ashry, Ph.D.

Named Award: Awesome Games Done Quick grant
Applicant Title: Associate Professor
Institution: University of Miami, Miami, FL
Project Title: CAFs: Biomarkers of Early Metastasis

Prevention is of utmost importance, and there is also an immediate need for the early detection of metastasis. We propose to establish Cancer-Associated Fibroblasts as a novel biomarker for the early detection of breast cancer metastasis.

General Audience Summary:

In recent years, the earlier detection of breast cancer has dramatically improved treatment success and clinical outcomes for breast cancer patients. Nevertheless, the lion’s share of deaths associated with breast cancer are due to disease metastasis, i.e., the spreading of breast cancer to grow in organ sites other than the breast, which can occur years or decades after initial therapy. The research we propose addresses an aspect of breast cancer therapy that is critical to improve the care and clinical outcomes for patients: early detection of disease progression and metastasis.

Cancer Associated Fibroblasts (CAFs), non-cancer cells that make up a large portion of a breast tumor, produce key factors involved in breast cancer initiation to progression, drug-resistance, and metastasis, and, critically, may be a target for therapeutic intervention in breast cancer of all stages. CAFs, as non-cancer cells, lack the ability that cancer cells have to adapt to targeted therapy, making them a very attractive therapeutic target. CAFs are present in every stage of breast cancer, including the most common type of non-invasive breast cancer, Ductal Carcinoma In Situ (DCIS). We have further determined that CAFs are a novel population of circulating cells (cCAFs) that are found in blood samples from almost all patients with metastatic breast cancer (Stage IV), in some patients with DCIS and Stage I-III disease, but not in patients who have undergone curative therapy for early-stage disease. CAFs play important roles in mobilizing breast cancer cells to more aggressive and metastatic behavior, and their presence in circulation suggests a role for them in establishing metastases.

We hypothesize that cCAFs are biomarkers indicative of breast cancer metastasis and thus may be a biomarker for early detection of metastasis.

Valsamo Anagnostou, M.D., Ph.D.

Partnership Award: IASLC/Prevent Cancer Foundation/Richard C. Devereaux
Applicant Title: Associate Professor
Institution: Johns Hopkins University, Baltimore, MD
Project Title: Comprehensive Genomic Analysis for Early Detection of Recurrence and Therapeutic Intervention in Stage I/II Non-small Cell Lung Cancer

This researcher offers a novel approach: she  will look for a biomarker with the potential to detect the recurrence of early-stage non-small cell lung cancer earlier than can current methods. This could lead to targeted treatment strategies.

General Audience Summary:

Lung cancer, predominantly non-small cell lung cancer (NSCLC), is the most common cause of death from cancer worldwide. The prognosis of NSCLC largely depends on tumor stage, and low overall survival rates are attributed to late diagnosis, when the tumor is either unresectable (cannot be completely removed by surgery) or metastatic. The relapse rate even in early-stage resectable lung cancer patients is in the range of 35-50% within 5 years after potentially curative treatment. Approaches to reduce lung cancer specific mortality include early detection of recurrence in patients with resectable disease by means other than radiographic surveillance. The latter is currently the gold standard for detection of recurrence; however, it remains limited in its efficacy for predicting outcomes in early-stage NSCLC patients. Prompt and accurate detection of recurrent disease delineates the need for additional imaging or diagnostic procedures and has immediate therapeutic implications.

It is therefore of great importance to develop sensitive and highly specific molecular markers that will improve the detection of recurrence in early-stage NSCLC patients and complement the predictive value of radiographic imaging. Recognizing the importance of genomic alterations in lung cancer biology, we hypothesize that there are tumor subsets in early-stage NSCLC with distinct somatic mutations, which reflect differences in clinical outcome. We propose a comprehensive genomic analysis of both the primary tumor as well as circulating cell-free DNA in order to identify genomic alterations associated with disease recurrence in early-stage NSCLC patients. This approach is highly innovative: the development of non-invasive molecular cancer biomarkers able to identify disease recurrence before any radiographic or clinical evidence could reshape treatment strategies and customize adjuvant therapy for early stage non-small cell lung cancer patients.

Susan Bullman, Ph.D.

Named Award: Figdor Family Fellowship in Cancer Prevention
Institution: Dana-Farber Cancer Institute

What she will study: Correlation of Fusobacterium Nucleatum Bacteria Strains and Colon Cancer Risk

Colorectal cancer (CRC) is responsible for approximately 694,000 deaths
annually worldwide. Recent studies revealed an enrichment of the bacteria Fusobacterium nucleatum (Fn) in CRC and demonstrated the potential of Fn to promote tumor formation in CRC animal models. Dr. Bullman and her team will identify the genomic differences between cancer and non-cancer associated Fn strains. “This analysis is likely to reveal subgroups among infected individuals who are ‘high-risk’ for developing colorectal cancer,” says Dr. Bullman. Identification of specific bacterial and host molecular signatures may reveal novel biomarkers for assessing CRC risk and facilitating early detection, diagnosis or prognosis in addition to novel drug targets for cancer prevention.

Derek Huffman, Ph.D.

Named Award: Marcia and Frank Carlucci Charitable Foundation Award in Cancer Prevention and Early Detection
Institution: Albert Einstein College of Medicine of Yeshiva University

What he will study: Efficacy of Prevention Strategies on the Cancer Aging Interface

While cancer is recognized as a disease of older persons, our understanding of how aging modulates cancer risk is not well understood. One major reason for this shortcoming is that most rodent models used to understand cancer prevention strategies tend to give rise to tumors while the rodents are still relatively young, rather than when they are older. Many studies show that tissue stem cells also cease to work as we age, and this dysfunction may contribute to diseases such as cancer. Dr. Huffman and his team will test how a well-known dietary (caloric restriction) and drug (rapamycin) intervention restore tissue function and prevent cancerous tumors utilizing specialized old mice and methods.

Divya Sahu, Ph.D.

Institution: University of California, San Diego

What she will study: Targeting of the Arginine-Nitric Oxide Pathway to Prevent Bladder Cancer Development

In the U.S., there were an estimated 74,690 new diagnoses and 15,580 deaths in 2014 due to bladder cancer. Bladder cancer starts with early abnormalities in the urothelium that cannot be easily diagnosed with current methods and progresses to non-invasive and invasive cancer. Dr. Sahu and her team have identified an increase in the metabolism of arginine – semi-essential amino acid, as well as this metabolism’s by-product of nitric oxide (NO) in bladder cancer. Dr. Sahu notes, “We hypothesize that arginine and downstream NO enhance bladder cancer cell survival, growth and invasion into surrounding tissue.” She and her team will investigate if targeting the arginine-NO components can stop bladder cancer development and/or growth.

Qiang Shen, M.D., Ph.D.

Named Award: Holden Family Research Grant in Breast Cancer Prevention
Institution: The University of Texas MD Anderson Cancer Center

What he will study: Impact of Novel Anti-Cancer Agents like HJC0152 on Breast Cancer Prevention

A pressing challenge in breast cancer care is the prevention of estrogen-receptor (ER)-negative breast cancer and triple-negative breast cancer (TNBC), as approximately 60 percent of breast cancers are not preventable with currently available selective ER modulators or aromatase inhibitors. Dr. Shen and his team will explore how a new class of anti-cancer agents they have developed, including HJC0152 and other compounds, can prevent these types of breast cancer. HJC0152 has demonstrated superior efficacy in inhibiting major signal transduction pathways, hindering TNBC cell proliferation and colony formation, suppressing the growth of xenograft and spontaneous mammary tumors and blocking ER-negative mammary tumor formation in animal models. This study will impact cancer prevention by investigating a new target and novel preventive agents that could lead to promising cancer preventive drug candidates for advanced preclinical development.

Xiaofeng Zhou, Ph.D.

Named Award: Lilly USA Research Award in Cancer Prevention and Early Detection
Institution: University of Illinois at Chicago
What he will study: Development of MicroRNA Biomarker Diagnostic Tools for Early Oral Cancer Prevention

Since 2003, deaths associated with oral cancer increased by about nine percent primarily because oral cancer is routinely discovered late in its development. Oral cancers are preceded by pre-cancerous lesions of which approximately 18 percent become cancer. New technologies are needed that can predict which lesions will make this transformation. Dr. Zhou and his team will examine archived pre-cancer tissue samples in order to identify genomic features (microRNA biomarkers) that are unique to pre-cancerous lesions. “These unique genomic features will provide us with molecular bases for early detection diagnostic tools of those aggressive lesions,” says Dr. Zhou

2015 Special Awards

Andrew Dannenberg, MD

Named award: Awesome Games Done Quick grant
Institution: Weill Cornell Medical College
What he will study: A blood test with the potential to diagnose women at increased risk of breast cancer

Dannenberg and his team will attempt to validate a blood-based signature of fatty tissue inflammation in the breast. This project could be a step toward developing a blood test that identifies women who are at increased risk of developing breast cancer. Dannenberg’s lab has long been exploring the relationship between inflammation and cancer. In recent work, he has used mice and human breast tissue samples to establish a link between obesity, inflammation and aromatase, a key enzyme involved in the production of estrogens. This is one of multiple potential mechanisms by which inflamed fat may increase the risk of breast cancer.

Maarten Bosland, D.V.Sc., Ph.D.

Institution: University of Illinois – Chicago
Named Award: Awesome Games Done Quick Research Grant in Prostate Cancer
What he will study: Prevention of Hormone-Induced Prostate Cancer

Prostate cancer is the most common (non-skin) cancer in men and the second leading cause of cancer death. Male sex hormones (androgens) are considered critical factors in prostate cancer development. Because estrogens are formed from androgens in males, it is conceivable that estrogens play a role in prostate carcinogenesis. Dr. Bosland and his team plan to collect preliminary data to examine how androgens and estrogens interact, as a possible point at which to interfere in the development of prostate cancer.

Sonia de Assis, Ph.D.

Institution: Georgetown University
Named Award: Holden Family Research Grant in Breast Cancer Prevention
What she will study: Paternal Obesity and Reprogramming of Breast Cancer Risk in their Offspring

Obesity is one of the few modifiable risk factors for breast cancer. Some studies show that a mother’s obesity and nutrition during pregnancy can also affect her daughter’s breast cancer risk; however, no studies have investigated the impact of a father’s obesity or dietary habits on breast cancer risk in his children using a rat model of the disease. Dr. de Assis and her team will investigate whether paternal obesity around the time of conception reprograms a father’s germ-line epigenome (chemical switches that turns genes on and off) and increases a daughter’s likelihood of developing breast cancer.

Ying Fu, Ph.D.

Institution: Georgetown University
Named Award: ONYX Pharmaceuticals Research Award
What he will study: Omega-3 Fatty Acids for Liver Cancer Prevention

Carcinogenesis of hepatocellular carcinoma (HCC) remains the third leading cause of cancer–related deaths worldwide. Currently, no biomarkers exist for early detection, and death occurs soon after diagnosis. Dr. Fu will test a potential biomarker, gamma-OH-Acr-dG, for the early detection of liver cancer and will also examine a mechanism-based method of using omega-3 fatty acids and the antioxidant from green tea as a novel combined cancer chemopreventive.

Ronan Kelly, M.D., M.B.A.

Institution: Johns Hopkins University
Named Award: Lilly USA Research Award in Cancer Prevention and Early Detection
What he will study: Targeting the hedgehog pathway in Barrett’s Esophagus using Itraconazole

Gastro-esophageal reflux disease (GERD) is one of the most common medical conditions in the United States and it is also a predisposing condition to esophageal adenocarcinoma (EAC), a lethal cancer with increasing numbers of new cases and a dismal 5-year survival rate. About 10% to 15% of patients with GERD develop Barrett’s Esophagus (BE), a well-established premalignant condition for EAC. Innovative endoscopic treatments have been shown to be safe and effective in the treatment of BE. But recurrent or resistant BE is not uncommon in some patients. Dr. Kelly and his team will build on the work of colleagues at Johns Hopkins to investigate if Hedgehog signaling is significant in recurrent/resistant BE and whether Itraconazole, a commonly used antifungal treatment, could be used as a chemo-preventive agent.

Ronac Mamtani, M.D., M.S.C.E.

Institution: University of Pennsylvania
Named Award: Figdor Family Research Award in Cancer Prevention
What he will study: The impact of metformin on the risk of prostate cancer

One strategy to reduce the risk of prostate cancer in the general population is the chemopreventive use of metformin, a commonly used diabetes medication. Dr. Mamtani and his team will determine whether metformin use is associated with a decrease in prostate cancer risk and less-aggressive prostate cancer compared to sulfonylureas, the common alternative therapy for diabetes. “The results of this study could lead to rapid clinical translation and future interventional trials of metformin for the primary prevention of prostate cancer in patients with and without diabetes,” Dr. Mamtani said.

Stacy Park, Ph.D., M.S.

Institution: University of California, Los Angeles
What she will study: The Role of E-cigarettes in the Pathogenesis of Lung Cancer

Little is known about the health effects of electronic-cigarettes (ECIGS), and yet they are sometimes advertised as safe alternatives to smoking. Data are needed on whether ECIGS cause cancer. Dr. Park and her team will assess whether normal lung cells exposed to ECIGs turn into cancerous cells. “We expect to be the first group to determine if ECIGs have the potential to cause cancer and to have information about which smokers will have negative health responses to ECIGs,” says Dr. Park. “By informing Food and Drug Administration ECIG policy, [our] research will have a significant impact on lung cancer prevention.”

Kathryn Taylor, Ph.D.

Institution: Georgetown University
Named Award: Richard C. Devereaux Outstanding Investigator Award in Lung Cancer Prevention
What she will study: Smoking Cessation in Lung Cancer Screening Participants

The United States Preventive Services Task Force recommends annual screening for lung cancer with low-dose computed tomography (CT) in adults ages 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Studies suggest that concurrent smoking cessation programs will be essential in order to achieve the full benefit of screening. Dr. Taylor and her team will develop and pilot test a telephone counseling cessation intervention. They will capitalize on the critical ‘teachable moment’ of learning of one’s screening result. “The long-term goal is to evaluate the telephone counseling intervention in a multisite intervention trial and ultimately, to disseminate it for use by lung screening programs,” says Dr. Taylor.

Sharon Pine, PhD

Institution: Rutgers, The State University of New Jersey
Named Award: The Richard C. Devereaux Outstanding Young Investigator Award in Lung Cancer Prevention

Lung cancer is the leading cause of cancer deaths worldwide, leading to 1.3 million deaths per year. Dr. Pine and her team will study whether a non-invasive blood test will predict those who are at increased risk of developing lung cancer. Their goal is to ultimately identify those at high risk, either before their cancer starts or when their cancer is in the earliest stages, when treatment is more likely to be successful.

Susan Steck, PhD

Institution: University of South Carolina
Named Award: Prevent Cancer Foundation – Living in Pink Grant

Inflammation is a normal biologic process that is necessary for healing wounds and combating infection. Unlike the normal inflammatory response, chronic inflammation appears to play a role in a number of chronic diseases, including cancer. Dr. Steck will examine the association between diet and inflammation with the use of a new dietary inflammation index in research on breast and colorectal cancers. The project may help to identify novel intervention strategies for cancer prevention.

Ligi Paul, PhD

Institution: Tufts University
Named Award: Holden Family Research Award in Breast Cancer

A common variation in the gene for the protein dihydrofolate reductase (DHFR) increases the risk for breast cancer in multivitamin users. Currently it is not known how the genetic variation in DHFR influences cancer risk in those who use folic acid containing supplements. Dr. Paul will study how genetic variations affect the body’s use of folic acid in ways that may increase cancer risk. The information generated by this project is necessary to adopt measures to reduce the cancer risk associated with this variation.

Josane Sousa, PhD

Institution: Vanderbilt University
Named Award: Speed Demos Archive Research Fellowship in Gastric Cancer

Stomach or gastric cancer is the second leading cause of cancer-related death worldwide. Dr. Sousa is looking at the potential for microRNAs to distinguish healthy individuals from individuals with pre-cancerous lesions and early-stage gastric cancer. This study could potentially lead to the development of minimally invasive tests that would improve the early detection of gastric cancer.

W. Martin Kast, PhD

Institution: University of Southern California Norris Comprehensive Cancer Center
Named Award: Genentech Research Award in Ovarian Cancer

Ovarian cancer ranks fifth in causes of cancer-related deaths in women and second among all gynecologic cancer-related deaths. There is an urgent need for innovative tools to identify asymptomatic women with early-stage ovarian cancer because most cases are diagnosed at advanced stages due to the lack of clinical symptoms. Dr. Kast will investigate a possible biomarker for early detection of ovarian cancer.

Joel Mason, MD

Institution: Tufts University
Named Award: Marvin M. Davis Research Award in Colorectal Cancer

Overweight and obesity have been convincingly implicated as factors that increase the risk of colorectal cancer. Dr. Mason will explore the means by which obesity promotes cancer risk in order to identify potential targets for cancer prevention. By defining the cellular pathways by which obesity affects the growth of colorectal cancer, we can arrive at strategies that will interrupt these pathways. The experiments will utilize several varieties of genetically-engineered mice to delineate these pathways and thus identify several potential targets for cancer prevention.

Meredith Tennis, PhD

Institution: University of Colorado

Lung cancer remains the leading cause of cancer death in the world for both men and women. Non-small cell lung cancer accounts for about 90% of lung cancer cases, with nearly 75% of them diagnosed with advanced, inoperable, or metastatic disease. Prevention studies have largely been ineffective. However, a recent chemoprevention trial of iloprost showed reduced degree of dysplasia in former smokers with six months of iloprost treatment. Frizzled 9 (Fzd9) is known to mediate the effects of iloprost and may be a marker that predicts response to iloprost chemoprevention. Dr. Tennis will study the possibility of Frizzled 9 as such a marker.

Vijayakrishna Gadi, M.D., Ph.D.

Institution: Fred Hutchinson Cancer Research Center
Named Award: Prevent Cancer Foundation – Living in Pink Grant

Researchers examine different markers of cancer risk in an effort to learn more about how the disease develops and how it can be prevented. The Foundation is supporting Vijayakrishna Gadi, MD, PhD, to research a less-studied marker of breast cancer risk, fetal microchimerism (a small number of cells that move from a fetus to a woman during pregnancy), which could lead to new opportunities for secondary prevention.

Yuriko Mori, M.D., Ph.D.

Johns Hopkins University, School of Medicine

Colorectal cancer is the second leading cause of cancer deaths in the U.S. for men and women combined. With screening, colorectal cancer can be prevented or detected early. Dr. Mori’s goal is to address the challenge to better identify those at highest risk of developing colorectal cancer—those with the greatest need of invasive colonoscopic screening or other preventive measures.  This grant is made possible by the Doornink Family Charitable Trust and Mrs. Cecile Tauzin.

Suzanne O’Neill, Ph.D.

Institution: Georgetown University
Named Award: Holden Family Grant in Breast Cancer

Mammographic breast density is a strong risk factor for breast cancer, yet there is little known about how aware women are of this risk factor. Would greater awareness increase their interest in risk management options such as chemoprevention or enhanced screening, such as MRI? The Foundation is funding Suzanne O’Neill, Ph.D., to assess cognitive, emotional and attitudinal variables related to breast cancer risk with a focus on breast density and management approaches. She will use this information to pilot an intervention aimed at increasing appropriate use of chemoprevention and enhancing screening to help prevent breast cancer in this high-risk group.

Bo Peng, Ph.D.

Institution: University of Texas, M.D. Anderson Cancer Center
Named Award: Richard C. Devereaux Outstanding Young Investigator Award in Lung Cancer Prevention  

Genetic risk factors have been identified for lung cancer, yet it is unclear how to make efficient use of individual genetic information for prevention and early detection of this disease. Foundation-funded researcher Bo Peng, Ph.D., is investigating whether it is cost-effective to use individual genetic profiles for the prevention of lung cancer. This research will provide valuable information regarding the utility of individual genetic information and will help in the development of personalized cancer prevention and treatment options.

Iris Romero, M.D.

Institution: The University of Chicago
Named Award: Figdor Family Research Grant

Studies have shown that Metformin, a commonly used treatment for Type-2 diabetes, decreases the risk of developing cancer. In Dr. Iris Romero’s preliminary studies in ovarian cancer, Metformin prevented tumor development in mice and inhibited proliferation of ovarian cancer cells. The Foundation is funding Dr. Romero to continue this research by clarifying the cancer prevention effect of Metformin in high-risk groups.

Yang Wang, M.D.

Institution: Dana-Farber Cancer Institute
Named Award: Foundation Partnership Award: IASLC Lung Cancer Fellowship Award

EML4-ALK fusion-type tyrosine kinase is an oncoprotein found in a subset of non-small cell lung cancer (NSCLC). Crizotinib, an FDA-approved small-molecule inhibitor of ALK, showed an impressive response rate as compared with second-line chemotherapy. Despite these promising results, disease relapse due to kinase inhibitor resistance is inevitable through secondary mutations or bypass signaling pathways. Dr. Wang’s research seeks to identify the various resistance mechanisms for ALK inhibitors and then to aid the development and design of new therapies for the treatment of NSCLC patients with ALK rearrangements.

Brian Rood, M.D.

Institution: Children’s National Medical Center
Named Award: Sarah Howard Childhood Cancer Fund for Our Children’s Health Grant

Medulloblastoma is the most common cancerous brain tumor in children, and brain tumors are the most common cause of cancer-related death in children. The Foundation is supporting the research of Brian Rood, M.D., to identify biomarkers for medulloblastoma that have the ability to reflect the response to therapy and/or disease reoccurrence. These biomarkers would be invaluable to the clinical management of this disease.

Derek Huffman, Ph.D.

Mentor: Nir Barzilai, M.D.
Institution: Albert Einstein College of Medicine of Yeshiva University

Over two-thirds of American adults are overweight or obese. Obesity is associated with increased risks of getting cancer, including colorectal cancer (CRC), and of dying from the disease. Studies suggest that abdominal obesity, as measured by waist circumference, is a stronger predictor of cancer risk and death than measures of general obesity. The Foundation is funding Derek Huffman, Ph.D., under the guidance of Nir Barzilai, M.D., to study whether removal of abdominal fat reduces tumors.

Surbhi Jain, Ph.D.

Mentor: Ying-Hsiu Su, Ph.D.
Institution: Drexel University

Many of the 520,000 lives lost to liver cancer each year could be saved with early detection. However, it is nearly impossible to detect liver cancer using current methods of detection. Recent findings show that tumor-derived DNA can be detected in urine. The Foundation is supporting Surbhi Jain, Ph.D., under the guidance of Ying-Hsiu Su, Ph.D., to develop a urine test for the early detection of liver cancer.

Jacobus Jansen, Ph.D.

Mentor: Jason Koutcher, M.D., Ph.D.
Institution: Memorial Sloan-Kettering Cancer Center

Patients diagnosed with head and neck cancer have a poor outcome when the cancer is detected too late. Early detection could reduce the number of patients dying of this disease. The Foundation is supporting Jacobus Jansen, Ph.D., under the guidance of Jason Koutcher, M.D., Ph.D., to use imaging techniques with a ‘smart probe’ to detect lesions in a precancerous stage (i.e. before they become cancer cells).

Sarah Adams, M.D.

Institution: University of Pennsylvania
Foundation Partnership Award: The ASCO Cancer Foundation 2009 Young Investigator Award in Ovarian Cancer

Dr. Adams’s work in the mouse has demonstrated that tumor-associated antigen-presenting cells (APC) from ascites are loaded with tumor antigens in vivo, and require minimal stimulation to function as powerful vaccines which can elicit a strong anti-tumor T cell response. Malignant ascites, present in most patients with advanced ovarian cancer, provides a uniquely accessible and rich source for tumor-experienced immune cells which can be used to construct inexpensive and effective immunotherapeutic regimens. The present application proposes to optimize an ascites-based protocol for active and passive immunotherapy for women with ovarian cancer. The results of this work will be used to design a phase I clinical trial of this treatment protocol.

Celine Mascaux, M.D., M.P.H.

Institution: University of Colorado Cancer Center
Foundation Partnership Award: IASLC Young Investigator Award

When lung cancer is detected early, it is more treatable and patients are expected to have a better outcome. So far, all screening strategies in high-risk populations have led to disappointing results. New, cheap, sensitive and non-invasive techniques for early diagnosis are urgently needed. The Foundation is supporting Celine Mascuax, M.D., M.P.H., in her research examining whether MicroRNAs found in plasma could be biomarkers for early detection of lung cancer.

Brian Sprague, Ph.D.

Institution: University of Vermont
Foundation Partnership Award: ASPO-American Society for Preventive Oncology/ Susan G. Komen

There is very little scientific evidence available for women who have had ductal carcinoma in situ (DCIS) and want to reduce their risk of breast cancer reoccurrence by making changes in their personal behaviors (physical activity, diet, etc.). Dr. Sprague will examine lifestyle factors of women who have had DCIS to determine if behaviors such as physical activity, abstaining from alcohol and avoiding weight gain make them less likely to face breast cancer reoccurrence. Dr. Sprague will also look at whether the effect of these activities on risk of reoccurrence depends on molecular features of the tumor.

2008 Fall Research Awardees

Matthew Carpenter, Ph.D.

Institution: Medical University of South Carolina

The tobacco industry has developed Potential Reduced Exposure Products (PREPs), which could possibly lower cancer risks. The Foundation is funding Matthew Carpenter, Ph.D., in his research examining one particular PREP to look at its effects on smoking behavior, overall tobacco exposure and motivation to quit. Ultimately, this study will guide smoking cessation programs and tobacco control efforts with the eventual aim to prevent and control cancer.

Yu Chen, Ph.D.

Institution: University of Maryland, College Park
Named Award: The Holden Family Fellowship in Breast Cancer

There is a critical need to develop better imaging technologies with high sensitivity and specificity to detect breast cancers for real time image guided biopsy. The Foundation is supporting Yu Chen, Ph.D., in his research to examine the combination of two promising tools for cancer prevention: optical imaging technologies and fluorescence molecular imaging. This research may potentially offer immediate information to clinicians and provide early detection of breast cancer.

Dallas Donohoe, Ph.D.

Mentor: Scott Bultman, Ph.D.
Institution: The University of North Carolina at Chapel Hill

Studies have shown that a high-fiber diet is correlated with reduced incidence of colorectal cancer (CRC), suggesting that dietary fiber may have preventive effects against cancer initiation. However, it is unknown how fiber protects against CRC. The Foundation is funding Dallas Donohoe, Ph.D., under the guidance of Scott Bultman, Ph.D., to research how a high- fiber diet prevents CRC, looking particularly at microbiota in the gut.

Ji Luo, Ph.D.

Institution: Bringham and Women’s Hospital
Foundation Partnership Award: AACR Prevent Cancer Foundation AstraZeneca Fellowship in Translational Lung Cancer Research

Cancer cells rely on both normal healthy genes and mutated ones. Using a technique called RNA interference, Ji Luo and his fellow researchers will reduce the production of thousands of normal proteins to determine which are required for cancer cells to survive. The researchers hope that, by decreasing these protein levels, cancer cells will die, while normal cells survive. The findings could lead to a new therapeutic approach by exposing a hidden set of new drug targets.

Janne Nappi, Ph.D.

Institution: Massachusetts General Hospital

Colon cancer (CRC) is the second leading cause of cancer deaths in the U.S. for men and women combined, yet it is largely preventable with screening. One screening method is computed tomographic colonography (CTC), which is effective in the detection of large, obvious lesions of the colon. However, CTC can miss the more subtle types of growths that appear flat. Foundation funded researcher Janne Nappi, Ph.D., is looking at ways to improve the accuracy of CTC so that those hard to see flat growths will be detected automatically by radiologists.

Gregor Reid, Ph.D.

Institution: The Children’s Hospital of Philadelphia

Leukemia is the most common cancer in children. Genetic abnormalities that contribute to childhood leukemia occur during fetal development, but the disease itself doesn’t develop for months to years after. Blood samples taken at birth could help identify risk of developing leukemia providing a window for preventing the disease. The Foundation is supporting the research of Gregor Reid, Ph.D., who is testing whether treating the disease before onset can selectively eliminate leukemic cells, thus preventing the disease.

Karen Sfanos, M.D.

Institution: Johns Hopkins University, School of Medicine

It is thought that chronic inflammation, perhaps due to the presence of infectious microorganisms, might contribute to prostate cancer development. The Foundation is supporting Karen Sfanos, M.D., under the guidance of Angelo De Marzo, M.D., Ph.D., in her research to identify “lesional” regions of microbial infections in the prostate and to correlate the lesions with prostate cancer incidence and/or inflammation. Identification of microorganisms in the prostate, and the correlation of microorganisms with inflammation of the prostate and/or prostate cancer will potentially have a major impact on prostate cancer prevention.

Chieu Tran, Ph.D.

Institution: Marquette University
Named Award: The Holden Family Fellowship in Breast Cancer

Mammography and MRI are widely used as screening tools for breast cancer, yet neither is a perfect system. A new imaging system that is less expensive and can rapidly and noninvasively detect breast cancer at an earlier stage with higher sensitivity, better spatial resolution and higher accuracy than currently available methods is needed. Thus, the Foundation is supporting Chieu Tran, Ph.D., whose research objective is to develop a novel and high performance instrument that can sensitively and accurately detect breast cancer cells at an earlier stage.

2008 Spring Research Awardees

Subhashini Jagu, Ph.D.

Mentor: Richard Roden, Ph.D.
Institution: Johns Hopkins University

Commercial HPV (human papillomavirus) vaccines currently only target two of the 15 known HPV types that cause cancer and these vaccines are expensive — costing over $300 per patient. The Foundation is supporting Subhashini Jagu, Ph.D., at Johns Hopkins University, under the guidance of Richard Roden, Ph.D., to develop a more cost-effective vaccine that protects more broadly against HPV infection, and ultimately, cervical cancer.

Animesh Barua, Ph.D.

Institution: Rush University

Catching ovarian cancer early increases patient survival by 80-90 percent, but currently there is no reliable technique to detect ovarian cancer in its initial stages. The Foundation is funding Amish Barua, Ph.D., at Rush University to combine enhanced ultrasound with a serum marker to create a reliable and sensitive screening method for ovarian cancer.

Maarten Bosland, D.V.Sc, Ph.D.

Institution: University of Illinois at Chicago

There is growing body of evidence to suggest that eating high levels of soy protein could reduce a man’s risk of developing prostate cancer. Maarten Bosland, D.V.Sc., Ph.D., at the University of Illinois at Chicago has been granted funding from Prevent Cancer to complete an ongoing Phase II clinical trial that studies the preventive effects of soy on the prostate. This study will seek to identify the critical links between eating soy and preventing prostate cancer.

Jed Fahey, Sc.D.

Institution: Johns Hopkins University

Individuals digest and absorb foods differently. Some researchers believe that people who efficiently convert glucosinolates, compounds from vegetables such as broccoli, cabbage and cauliflower, into isothiocyanate compounds, might benefit more from the anticancer properties of these vegetables. The Foundation is funding Jed Fahey, Sc.D., at Johns Hopkins University to study the concept that a person’s diet and the bacteria in his or her gastrointestinal tract may determine how much of a prevention boost he or she can receive from consuming fruits and vegetables. This project could take the first step in correlating disease incidence with gastrointestinal metabolism.

M. Naomi Horiba, M.D., M.P.H.

Mentor: Martin Edelman, M.D.
Institution: University of Maryland
Foundation Partnership Grant: IASLC Young Investigator Award

Lung cancer is the leading killer of both men and women in the U.S. Because tumor progression is associated with immune dysfunction, one approach to improve the survival of lung cancer patients is by targeting tumor associated immune dysregulation. The hypothesis of this proposal is that the suppression of the normal immune response in patients with non small cell lung cancer (tumor tolerance) is a critical determinant of patient outcome. Dr. M. Naomi Horiba, under the guidance of Dr. Martin Edelman, will investigate whether inhibiting the regulatory molecule COX-2 leads to a decrease in MDSCs (a cell type known to promote tumor tolerance) and thus a decrease in the ability of the tumor to grow.

Lauren Trepanier, D.V.M, Ph.D.

Institution: University of Wisconsin – Madison

Studies have suggested that certain lifestyle choices, such as smoking tobacco and eating charred meats, might increase a patient’s risk for breast cancer by introducing cancer-causing chemicals into the patient’s body. Prevent Cancer grant recipient, Lauren Trepanier, D.V.M., Ph.D., at the University of Wisconsin – Madison has a theory to explain those findings. She will study two enzymes found at varying concentrations in breast tissue that may render these chemicals harmless. Trepanier will examine if women with low levels of these enzymes are at higher risk for breast cancer. These studies could improve patients’ understanding of their risk of breast cancer and may help patients make lifestyle choices.

Pak Kim Wong, Ph.D.

Institution: University of Arizona

Studies suggest that the protein Nrf2, which regulates the body’s natural defenses, could be a key target for cancer prevention drugs. The Foundation supports Pak Kin Wong, Ph.D., at the University of Arizona in Tucson in his efforts to develop a rapid screening system for identifying new compounds that affect Nrf2 and the body’s natural cellular defenses. Understanding how these chemopreventive compounds work could be a leap forward in the prevention of many types of cancer. Additionally, this study will provide valuable information about the regulation of important genes.

Karen Wernli, M.D., Ph.D.

Mentor: Polly Newcomb, Ph.D., M.P.H.
Institution: Fred Hutchinson Cancer Research Center
Foundation Partnership Grant: American Society for Preventive Oncology (ASPO)

More women every year are living with a diagnosis of breast cancer, and each survivor hopes to make choices which positively influence her survival. The Foundation is supporting Karen Wernli, M.D., Ph.D., under the guidance of Polly Newcomb, Ph.D, M.P.H, to study how medications and vitamins affect death from breast cancer. The researchers believe that use of aspirin and non-aspirin-like medications and vitamins will lead to fewer deaths from breast cancer and that use of antidepressants will lead to more deaths from breast cancer.

Yanping Zhang, Ph.D.

Institution: University of North Carolina in Chapel Hill

Identifying genes involved in breast cancer  development is key to developing new medications that target the cancerous cells and to improving genetic screening guidelines. The Foundation is supporting Koji Itahana, Ph.D., at the University of North Carolina in Chapel Hill to study the role of a protein, p32, in killing breast cancer cells and preventing tumor formation. This work may increase our understanding of breast cancer genetics and lay the groundwork for identifying a new gene to help physicians assess cancer risk in patients.

Note: Originally awarded to Koji Itahana, Ph.D., who conducted the first year of research before leaving UNC-Chapel Hill, this grant was transferred to and completed by Yanping Zhang, Ph.D.

2007 Fall Research Awardees

Laura Fejerman, Ph.D.

Mentor: Elad Ziv, M.D.
Institution: University of California, San Francisco

Although African American women have a lower incidence of breast cancer compared to white women, their mortality rate is higher. Some African American women are diagnosed with tumors that are more aggressive and more difficult to treat. The Foundation is supporting Laura Fejerman, Ph.D., at the University of California, San Francisco, under the guidance of Elad Ziv, M.D., to improve the understanding of tumor variability among African American breast cancer patients.

Joelle Hillion, Ph.D.

Mentor: Linda Resar, M.D.
Institution: Johns Hopkins University

By turning off one gene, HMGA1, researchers have found that human uterine cancer cells seem to grow like normal cells. This finding and others suggest this gene is a promising target for preventive uterine cancer drugs. Scientists have identified agents, such as COX2-inhibitors and green tea extracts, that may block some HMGA1 pathways. The Foundation is funding Joelle Hillion, Ph.D., at Johns Hopkins University, to work under the guidance of Linda Resar, M.D., on a project investigating these novel agents to prevent uterine cancer via the HMGA1 pathway.

Olga Gorlova, Ph.D.

Institution: M.D. Anderson Cancer Center

Only a fraction of long-term smokers developing lung cancer; so the ability to focus screening efforts in a high-risk subgroup could have great potential. The Foundation is funding Olga Gorlova, Ph.D., of M.D. Anderson Cancer Center in Houston, in her efforts to estimate the benefit of lung cancer screening among high-risk individuals and to identify an optimal screening strategy for larger populations based on individual risk profiles.

Courtney Gray-McGuire, Ph.D.

Institution: Case Western Reserve University

Less than five percent of all cases of colon cancer can be attributed to known genetic mutations. Identifying and monitoring other genes involved in colon cancer may pave the way for early detection. The Foundation supports Courtney Gray-McGuire, Ph.D., at Case Western Reserve University in Cleveland in her efforts to locate a colon cancer susceptibility gene on chromosome nine.

Zhenhua Liu, Ph.D.

Institution: Tufts University

There is a growing body of evidence to suggest that regularly including folate in the diet can reduce colorectal cancer risk. Folate is a key player in keeping DNA healthy, so it is likely that studying folate-dependent pathways will help identify new ways to prevent colorectal cancer. The Foundation is funding Zhenhua Liu, Ph.D., at Tufts University in Bedford, Mass., to examine folate-specific genetic pathways and early tumor growth and development.

Giovanni Pitari, M.D., Ph.D.

Institution: Thomas Jefferson University

People in underdeveloped countries, with a high risk of exposure to specific intestinal toxins from bacteria, seem to be protected from colorectal cancer. These toxins are known to potently activate guanylyl cyclase C, a protein inhibiting to intestinal tumor formation in mice. The Foundation is supporting Giovanni Pitari, M.D., Ph.D., at Thomas Jefferson University in Philadelphia, in his work to study the role of guanylyl cyclase C as a molecular target to prevent colorectal cancer.

Habtom Ressom, Ph.D.

Institution: Georgetown University

Worldwide, as many as 500,000 people are diagnosed with hepatocellular carcinoma, a common liver cancer, each year. The low five-year survival rate of 11 percent, as reported by the American Cancer Society in 2008, is likely because the cancer is identified in advanced stages, too late for effective treatment. The Foundation is funding Habtom Ressom, Ph.D., of Georgetown University in Washington, D.C., to identify biomarkers for the early detection of liver cancer.

Daniel Rodriguez, Ph.D.

Institution: University of Pennsylvania

The vast majority of adults who smoke picked up their first cigarettes during their teenage years. By the time they turned 18, they were regular smokers with a growing risk of lung cancer. By understanding factors that keep adolescents from beginning to smoke and progressing to regular smoking habits, more effective and practical smoking prevention programs can be developed. The Foundation is funding Daniel Rodriguez, Ph.D., of the University of Pennsylvania, to examine the effect of “antismoking parent practices” on adolescent smoking.

Xiaofeng Zhou, Ph.D.

Institution: University of Illinois – Chicago

Oral cancer often goes unrecognized until its late stage where surgery can be less successful and more disfiguring. Most patients with oral cancer first had oral lesions which then became cancerous. But not all lesions are a sign of cancer: only 18 percent ever become cancerous. Differentiating between these types of lesions at an early stage could be key to saving lives. The Foundation is funding Xiaofeng Zhou, Ph.D., at the University of Illinois – Chicago, to identify the biomarker differences between the oral lesions that become cancerous and those that do not.

2007 Spring Research Awardees

Pamela Beatty, Ph.D.

Mentor: Olivera Finn, Ph.D.
Institution: University of Pittsburgh

This project focuses on combating inflammatory bowel diseases and their associated increased risk for developing colorectal cancer, the second-leading cause of cancer death in the Western world. Ulcerative colitis and Crohn’s disease are two conditions that are recognized as risk factors for colorectal cancer and as yet are uncurable. In their research, Drs. Beatty and Finn will explore the potential of creating a preventive vaccine that would boost the immune system to better recognize and eliminate tumor cells. They hope the vaccine will eventually be used to prevent the onset or recurrence of colorectal cancer and treat chronic colitis, and they expect that the data they generate from this study will support further research in clinical trials.

Xiang-Lin Tan, Ph.D.

Mentor: Simon Spivack, Ph.D.
Institution: Health Research, Inc./New York State Department of Health

Lung cancer is a leading cause of cancer deaths of both men and women in the United States and all over the world. Working off of recent research findings that show a diet high in fruits and vegetables plays a role in combating carcinogenic progression, this project will examine the specific molecular mechanisms responsible for shutting down harmful oxidants. Drs. Tan and Spivak will develop an in vitro monitoring system that closely watches one particular protein in hopes that it may eventually lead to new system for screening potential chemopreventive agents for lung cancer.

Jennifer Warren, Ph.D.

Mentor: Kola Okuyemi, Ph.D.
Institution: University of Minnesota – Twin Cities

Cigarette smoking rates among urban African Americans are unacceptably high. Although African Americans smoke fewer cigarettes daily, they experience higher rates of lung cancer than other ethnic groups. Though many African Americans want to stop, they are less likely to seek help and therefore are less successful than their white counterparts in their attempts to quit smoking. As a way to overcome some of the barriers faced by African Americans who want to quit smoking, Drs. Warren and Okuyemi will explore using an Internet-based intervention tool. Research shows African Americans use the Internet just the same as other groups, and the scientists hope this tool will be an accessible way for African Americans to receive this help. This study is designed to serve as a pilot for large clinical trials for smoking cessation interventions in African American smokers.

Katherine Crew, Ph.D.

Institution: Columbia University

Breast cancer is one of the most deadly cancers to affect women, and though significant strides have been taken to lessen the death toll, it still remains a main cause of cancer death. Currently, tamoxifen is the only FDA-approved drug to reduce the risk of developing breast cancer, however due to its side effects, it has not been used extensively. In building on existing clinical data, Dr. Crew will monitor the progress and biomarkers of 20 high-risk women who will take Vitamin D supplements during the course of this study. It is believed that Vitamin D may induce a preventive effect, and Dr. Crew hopes the results of this study lead to larger-scale trials to evaluate the potential of using high doses of Vitamin D in the prevention of breast cancer.

William Klein, Ph.D.

Institution: University of Pittsburgh

Colorectal cancer remains the second leading cause of cancer death in the U.S. despite recent gains in the rates of screening. Many people continue to be off-schedule for their recommended screenings, leading to many cases being diagnosed at much later stages when it is more difficult to treat. Though there are certainly a number of reasons for this, Dr. Klein will specifically study the way screening messages are delivered to encourage individuals over age 50 to get the tests. He will frame messages to see if people respond more favorably to learning what they could gain from the tests or what they could lose by not getting the tests. The goal is to learn which one is the more persuasive way of framing the message to stay on schedule with screenings, hopefully leading to a better understanding of how to best promote the message.

Barbara Schneider, Ph.D.

Institution: Vanderbilt University Medical Center

For nearly 30 years, the scientific community has known that a particular substance found in high concentrations within broccoli, and specifically broccoli sprouts, helps cells bolster their own defenses against cancer-causing agents. Dr. Schneider will test this substance, sulforaphane, to see how it responds when battling stomach cancer cells directly. By studying the RNA from the cells that are introduced to the broccoli sprout extract, she will be able to monitor the biochemical changes that occur within the affected genes. Dr. Schneider hopes this work will offer further understanding of what happens to proteins when combated directly with this beneficial compound.

Amanda Marzo, Ph.D.

Mentor: Andres Jaramillo, Ph.D.
Institution: Rush University Medical Center

Despite of improvements in therapy, the survival of breast cancer patients with advanced or metastatic disease is still very poor. This demonstrates the need for new approaches in therapy and identification of high-risk individuals. Dr. Jaramillo will investigate the breast cancer marker mammaglobin-A and see if its recognition by cancer-fighting lymphocytes produces a protective immune system response to breast cancer. Dr. Jamarillo hopes these studies could lead to the development of a breast cancer vaccine that would ramp up the body’s natural defenses.

Raymond Konger, Ph.D.

Institution: Indiana University – Indianapolis

Sun exposure is the leading cause of skin cancer, both melanoma and non-melanoma. Though melanoma is the more deadly of the two, non-melanoma skin cancers still pose a significant risk, especially to those with compromised immune systems. This research will examine a specific cellular protein, that when turned on by UV light, is critical to the formation of skin cancer. When activated, this protein causes a chain of events which results in cancer activity. Dr. Konger will explore the potential of using a drug to block this protein activation, thereby producing a chemopreventive effect.

2006 Fall Research Awardees

Betty Doan, Ph.D.

Mentor: Giovanni Parmigiani, Ph.D.
Institution: Johns Hopkins University

This project focuses on lung cancer. To make screenings such as CT scans and chest x-rays more accurate for early detection of lung cancer, Drs. Doan and Parmigiani aim to create a risk prediction model for lung cancer. The risk prediction model will be able to identify those at greatest risk for developing lung cancer. The model will use family and smoking history to estimate risk scores, the chance of having disease or a disease mutation. The risk score will be used in a screening decision tool to identify optimal ages to start a screening regimen and the optimal test frequency that corresponds to the highest chance of detecting disease. The risk score will also be used to identify families that may be more genetically caused (i.e., higher scores) to enhance the ability to find disease gene locations. Knowing these locations will help identify the disease gene, and genetic testing can then be offered. This risk prediction model and screening tools that identifies individuals at greatest risk will increase the early detection rate and ultimately disease curability.

Gabriela Ion, Ph.D.

Mentor: W. Hardman, Ph.D.
Institution: Marshall University

Dr. Ion and Dr. Hardman’s study will investigate one possible protective mechanism of two food components, n-3 and n-6 Fatty Acids (FA), on breast cancer development. It hypothesizes that n-3 FAs (present in canola oil) versus n-6 FAs (present in corn oil) will disrupt the signaling events between breast tumoral cells and adjacent cells, in this casepreadipocytes, by decreasing the level of pro-inflammatory cytokines to aid cancer prevention. This study may help to understand the effect of dietary changes at a cellular level. A better understanding of n-3 FAs mechanisms for suppression of tumorigeneses may lead to dietary recommendations that could reduce the incidence of cancer for future generations.

Jung Eun Lee, Sc.D

Mentor: Edward Giovannucci, MD, Sc.D
Institution: Brigham and Women’s Hospital – Channing Laboratory

The underlying hypothesis is that folate deficiency and low intake of vitamin D are associated with increased risk of colorectal cancer and polyps early in carcinogenesis. The protective role of vitamin D against colorectal cancer risk has been strongly debated since a clinical trial study of vitamin D and calcium showed no benefit on colorectal cancer. This study aims to examine if dose and timing of folate and vitamin D intake are associated with colorectal cancer risk. The proposed research has the potential to help explain some of the disparate results that have been reported in this area. Adding to the conflicting data on risk factors for colorectal cancer would be an important contribution.

Mark Rubinstein, Ph.D.

Mentor: Ananda Goldrath, Ph.D.
Institution: University of California, San Diego

Dr. Rubinstein and Dr. Goldrath’s research project has the potential to make an impact in the development of preventive cancer vaccines. This project proposes to augment primary immune responses using a novel vaccine component that we have previously developed. Specifically, researchers will take a natural substance found in the body, which can stimulate the immune system, and increase its biological activity over 50 fold. It is believed that incorporation of this novel stimulatory agent into vaccine design will lead to dramatically improved immune protection and aid in the development of preventative cancer vaccines.

David Stachura, Ph.D.

Mentor: David Traver, Ph.D.
Institution: University of California, San Diego

The goals of this study are to explore the molecular signature of hematopoietic stem cells inzebrafish and determine pathways leading to their oncogenic transformation. The experiments proposed in this fellowship will aid in understanding an important stage ofhematopoietic development especially sensitive to leukemic transformation. Knowledge gained from this research will help us to understand leukemic initiation and progression, lead to improved diagnostic tools and treatment strategies for patients, and aid in preventing leukemia. The zebrafish model provides a practical approach to dissecting specific genes and applying them to the human condition.

Fellow: Jean Tang, Ph.D.

Mentor: Ervin Epstein, M.D
Institution: Children’s Hospital & Research Center, Oakland

The proposal will determine if vitamin D and/or statins can prevent basal cell carcinoma (BCC) of the skin in mice. The researchers propose to perform the first in vivo experiments where they will feed vitamin D and statins to mice to assess whether these drugs may prevent BCC tumors from forming on their skin. The proposed studies will clarify the role of sunlight, vitamin D, and diet for prevention of the most common cancer in the U.S. This work could have large impact on cancer prevention through easily obtainable means – oral or topical vitamin D and statins.

Wenli Cai, Ph.D.

Institution: Massachusetts General Hospital

Dr. Cai’s research proposes a non-cathartic approach to Computedtomographic colonography (CTC), aka virtual colonoscopy. The approach of CTC is based on the combination of fecal tagging with orally administered contrast agents and post-acquisition electronic cleansing (EC) of tagged fecal materials. A non-cathartic approach to CTC has the potential to revolutionize colon screening. The main technical barrier is the lack of an effective EC scheme for electronic cleansing the tagged fecal materials. In this project we will develop and evaluate an advanced EC scheme for interpretation of CTC images of patients examined with non-cathartic bowel preparation. This EC-aided non-cathartic CTC examination may permit colon screening to be performed without the use of pre-examination cathartic bowel cleansing, thus providing a highly-acceptable alternative to patients and highly accurate tool for diagnoses.

Chun Liu, M.D.

Institution: Tufts University

Large epidemiologic studies across regions and populations have consistently shown that beta-cryptoxanthin is associated with a reduced risk of developing lung cancer, particularly among current smokers. However, the molecular mechanisms by which beta-cryptoxanthinaffects lung carcinogenesis are poorly understood. This study proposes to examine thechemopreventive effect of beta-cryptoxanthin supplementation in both low- and high-dose on cigarette smoke-induced lung carcinogenesis in ferrets by measuring molecular markers, including p53 tumor suppressor gene (which plays a critical role in suppressing lung carcinogenesis), p53 target genes, cell growth, programmed cell deaths in the lungs of ferrets, and by examining lung oxidative stress and oxidative DNA damage and lung pathological changes. Data from this study will provide important information for the evaluation of the potential usefulness of beta-cryptoxanthin as a chemopreventive agent against the development of lung cancer.

Jong Park, Ph.D.

Institution: H. Lee Moffitt Cancer Center & Research Institute

Dr. Park’s research represents a novel approach to develop a highly sensitive probe to detect DNA methylation. In this proposal, the researchers will prepare templates for aptamer(molecular probes which are man-made, flexible, and are single-stranded DNA) selection and counter-selection, and capture these templates by synthesizing other man-made molecules called peptide nucleic acids (PNAs). Aptamers will be useful to recognize the complexes assembled by the cell for epigenetic silencing. Templates made by this research will later lead to identification of small molecule aptamers that detect the com
plexes responsible for tumor suppressor gene silencing in cancer. In the future, high-throughput panels of aptamersagainst silenced tumor suppressor and repair genes in biopsy and non-invasive samples (e.g. blood, sputum, and urine) could create the potential for highly effective cancer screening, early detection, therapeutic monitoring and prevention.

Robert Strange, Ph.D.

Institution: University of Colorado

Moderate exercise has recently been linked to a decreased risk of cancer; however, the mechanism responsible for the decreased risk is not understood. Dr. Strange’s research proposes that, with exercise, angiogenesis will preferentially be increased in muscle, and blood flow will be directed and redistributed to muscle. Conversely, it is hypothesized that exercise will result in decreased angiogenesis and reduced blood supply in the tumor. This will in turn lead to an increase in tumor cell death, slowed tumor growth, and tumor regression. This study represents a first attempt to evaluate the effect of exercise on breast cancer progression by examining the mechanism responsible for exercise-mediated tumor growth inhibition.

Marilyn Tseng, A.M., Ph.D.

Institution: Fox Chase Cancer Center

Dr. Tseng will examine associations among central adiposity, adiposity-related “thrifty genes,” and breast density among foreign-born US Chinese women. Because of its strong association with breast cancer, higher breast density, measured from a mammogram, is thought to be a useful marker for breast cancer risk. The work will be conducted using data collected from a separately funded study on breast density in recently immigrated US Chinese women. The ~300 participants in that study are pre-menopausal, age 40 years and up, with US residence of 12 years or more. Data collection includes interviews; body measurements; DNA samples; and a screening mammogram assessed for breast density. The proposed work will add on genotyping and statistical analyses to investigate associations among genes of interest, central adiposity, and breast density. Findings from the proposed work will be relevant to breast cancer prevention in all women regardless of ethnicity. Findings could clarify whether reducing fat accumulation during adulthood can prevent breast cancer; improve our ability to predict risk based on genetic characteristics; and identify women who may be genetically susceptible to both central adiposity and breast cancer.

Xiangsheng Zuo, Ph.D., M.D.

Institution: University of Texas, M.D. Anderson Cancer Center

Dr. Zuo’s proposal seeks to examine the role of a specific protein (PPAR-delta) in tumor formation in the colon. Evidence has been found supporting the idea that PPAR-d promotes the formation of colon tumors, but data from some other research groups have shown that PPAR-d might have the opposite or no effects. The work proposed in this research project aims to test the effects of genetically stopping the production of PPAR-d in the mouse intestine on tumor formation. The results of this proposal will provide needed information not only to determine whether PPAR-d has a role in developing chemopreventive agents against cancer but also to ensure that drugs used to treat other diseases by stimulating the function of PPAR-d are safe for use.

Jin-Rong Zhou, Ph.D.

Institution: Beth Israel Deaconess Medical Center

Scientific evidence suggests that dietary intake of soy or black tea individually may have a potent anti-prostate cancer effect. Dr. Zhou will investigate this evidence further by looking at the combination of soy and black tea as a potential dietary target for prostate cancer prevention. Dr. Zhou will examine if the dietary combination will significantly inhibit development and progression of prostate cancer in a synergistic manner. The results of this research, along with evidence from previous studies, could lead to further studies of men at high risk for prostate cancer and eventually to a realistic prostate cancer prevention strategy.

Eduard Chekmenev, Ph.D.

Institution: Huntington Medical Research Institutes

Dr. Chekmenev’s research proposes a non-invasive approach to early detection and diagnosis of breast cancer that capitalizes on the metabolic differences between tumors tissue and normal tissue. Dr. Chekmenev and his team will use a technique they have developed called PASADENA, which has brought magnetic resonance molecular imaging to within striking range of the sensitivity of other molecular imaging techniques. This work could lay the foundation for early diagnosis of breast tumors, which would significantly improve breast cancer prevention and early treatment.

2006 Spring Research Awardees

The first cycle of research grants and fellowships of 2006 produced nine awards for research in the categories of liver, colon, breast, cervical, and prostate cancers, as well as studies into behavioral patterns that lead to low cancer screening rates.

Yanming An, Ph.D.

Mentor: Radoslav Goldman, Ph.D.
Institution: Georgetown University Medical Center

These researchers are seeking to define reliable biomarkers of hepatocellular carcinoma (HCC), a serious and complicated chronic liver disease that may lead to liver cancer, in order to detect and track the illness through therapy. HCC ranks fifth in cancer incidence and causes the death of about half a million people worldwide annually. The incidence of HCC in the United States is increasing, most likely due to the rise of hepatitis C. HCC develops because of complex changes in genes and in the expression of proteins in the blood. Drs. An and Goldman believe these proteins may serve as “markers” that signal HCC and could be used for early detection. In this study, the researchers hope to identify these HCC-related proteins and define new methods for their detection in the blood. This information could lead to a powerful diagnostic test, which could be used not only for early detection of HCC, but also for tracking of the progression of disease and the effectiveness of therapy.

Sachidanand Hebbar, Ph.D.

Mentor: Deanna Smith, Ph.D.
Institution: University of South Carolina

Drs. Hebbar and Smith are testing the effects of common Type 2 diabetes medications on preventing or encouraging the incidence of colon cancer. The cells that line the colon are unusual because they are exposed to ingested substances in our diet. These cells can also be directly influenced by oral medications and this unique feature offers opportunities for chemoprevention. Drs. Hebbar and Smith are investigating one type of drug, called “a PPAR-activating drug,” to determine its cancer preventive abilities. PPARs, or peroxisome proliferator-activated receptors, are a group of hormone receptors belonging to the steroid family. Researchers have discovered that some colon cancer cells have mutant PPARs. PPAR-activating drugs, used to treat patients with type 2-diabetes, have been shown to both protect the hormones and provide some protection from colorectal cancer in laboratory tests. However, when used on mice with human-inherited colon cancer (FAP), the drugs actually worsened the tumors. These researchers hope to discover why this occurs, and who may benefit from these drugs. This is important not only for colon cancer patients, but also for more than 1.5 million patients in the United States prescribed supplemental PPAR drugs in addition to insulin to control diabetes.

Bruce Ling, M.D., MPH

Institution: University of Pittsburgh

Colorectal cancer is the second leading cause of cancer death among Americans. Screening is an effective way of detecting the disease early and improving the chance for cure. Unfortunately, only about half of eligible Americans are following recommended screening guidelines. Despite a number of initiatives to improve screening rates, there has been little success. One promising area not yet well studied is the way health care providers and patients discuss colorectal cancer screening with each other. In this study, Dr. Ling is testing a method to improve doctor-patient communication by encouraging patients to bring up the topic at clinic visits and by providing an information sheet that patients can review with their doctors. His theory is that by improving communication on colorectal cancer screening to patients, Americans will adopt this cancer prevention behavior and the burden of colorectal cancer can be minimized in this country.

Lisa Madlensky, Ph.D.

Institution: University of California, San Diego

Dr. Madlensky is developing informational materials for patients who are diagnosed with colon polyps – an early precursor to colon cancer – as a way for those patients to talk to their family members who may also be at risk. She will also study whether or not polyp patients are advised to make lifestyle changes such as diet or exercise. People who have small growths in the colon, called polyps, are at higher risk of developing colorectal cancer (CRC) than the average person. For some specific types of polyps, there is also an increase in risk for the close relatives of the person with the polyp. But not all polyp patients are aware of this increased risk for their family members or the need for close relatives to be screened. This project will develop materials to be provided by physicians to their polyp patients to help them communicate the details of their polyp diagnosis to their relatives. In turn, these relatives can share the polyp information with their own doctors, and together they can decide on the best CRC screening approach for them. Dr. Madlensky will also examine whether polyp patients are being advised to make the lifestyle changes that can reduce the risk of having more polyps in the future.

Ehsan Samei, Ph.D.

Institution: Duke University Medical Center

Mammography is currently the most reliable screening technique used for breast cancer detection. However, this method of screening has difficulty visualizing masses and micro-calcifications hidden in dense tissue. Normal tissue, called anatomical noise, can prevent radiologists from seeing important changes in dense breast tissue. Acquiring two views of each breast can help radiologists eliminate this problem, but taking two views requires two separate, uncomfortable compressions of the patient’s breast. Moreover, the image data from the two views cannot be directly compared. This study is investigating the feasibility of a new imaging procedure, called Stereo Imaging (SI), in which two digital radiographic images of the breast are acquired using a single compression. The SI method produces three-dimensional X-ray images with stereo views of the possible breast lesions and has the potential to be easily translated into clinical settings.

Hua Su, Ph.D.

Mentor: Careen Tang, Ph.D.
Institution: Georgetown University, Lombardi Cancer Center

These researchers are investigating the cooperative role two cancer genes have in developing and progressing breast cancer. By studying the early stages of breast cancer at the molecular level, the doctors hope to offer an important prevention and prediction tool for high risk patients. Preventing breast cancer requires a better understanding of the biological abnormalities that lead to its development and progression. Understanding early-stage breast cancer progression at the molecular level will provide vital information for early diagnosis and prevention. We do know that one oncogene (cancer-causing gene), ErbB-2, and one metastasis (cancer-spreading) gene, CXCR4, are involved in the progression of breast cancer and the spread of the disease to distant organs outside the breast. But neither of these factors alone is enough to initiate the development of breast cancer. In this proposal, Drs. Su and Tang will investigate how these two genes work together in breast cancer. These studies will provide crucial information that may be used to predict women at high risk for developing the disease.

Erin M. Siegel, Ph.D.

Institution: H. Lee Moffitt Cancer Center and Research Institute

Dr. Siegel is examining a biomarker that indicates damaged genetic material as a way to predict which women infected with the Human Papillomavirus (HPV) are most likely to develop cervical cancer, as not all HPV infections progress past the initial exposure. Infection with certain types of HPV, or high-risk HPV types, may lead to cancer of the cervix. But because many high-risk HPV infections are cleared and do not lead to disease, testing for HPV infection may not be the best way to find women at risk for cervical cancer. Dr. Siegel hopes a marker found in blood that is an an
tibody to damaged genetic material will prove an effective early detection and prevention tool. Dr. Siegel hopes to determine whether this new marker is different among women with an HPV infection compared to women without an infection. Results may help improve cervical cancer prevention efforts worldwide.

Gang Zeng, Ph.D.

Institution: University of California, Los Angeles

Dr. Zeng is investigating new biomarkers that could detect the difference between prostate cancer and other prostate abnormalities that are non-malignant. The research will hopefully yield a molecular tool that would complement the PSA test given to detect prostate cancer early, minimizing false positives and negatives. In prostate cancers, the use of prostate-specific antigen (PSA) screening has led to the earlier detection of malignancy. However, the test has limitations because increased PSA levels also could indicate nonmalignant conditions, such as prostatic hyperplasia or prostatitis. More specific prostate cancer markers are needed. Dr. Zeng is examining autologous antibodies (Ab) as a possible marker for the disease. Such antibodies have been found in the blood of prostate cancer patients and are easy to detect through a non-invasive and cost-effective blood test. Dr. Zeng’s long-term goal is to establish an approach that would complement the PSA test as a tool for early detection of prostate cancer.

Alicia Matthews, Ph.D.

Institution: University of Illinois, Chicago

In this study, Dr. Matthews will examine the effects of a computer-based intervention system designed to increase cancer screening awareness in lesbian, gay, and bisexual (LGB) women and men. The LGB community currently has a proportionally higher incidence rate of late diagnoses due to low cancer screening rates. Lesbian, gay and bisexual women and men are at risk for a late diagnosis of cancer because of low cancer screening rates. Still, little is known about the barriers to cancer screening in these individuals. Even less is known about how to increase their cancer-screening behavior. This study will first adapt an existing computer-based Tailored Intervention Messaging System (TIMS) cancer screening intervention for use with these individuals and then pilot test it in a sample group to determine whether it is feasible, accepted and effective in prompting screening. Results of this study will provide data that could lead to a large, randomized controlled behavioral trial in this population.

2005 Fall Research Awardees

Maarten C. Bosland, D.V.Sc., Ph.D.

Institution: New York University School of Medicine

In this cancer prevention clinical trial, men who have had prostate cancer will receive a dietary intervention of soy protein for two years following surgery. Researchers hope to determine whether soy can help prevent recurrence of prostate cancer in men who are at high risk. Recurrence of prostate cancer is actually the growth of tumor cells left behind following a radical prostactectomy. If the study shows that soy can prevent recurrence, it is also likely to prevent the  growth of these small primary cancers.

Han Chang, Ph.D., M.D.

Institution: University of Pittsburgh

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are primary liver cancers with high death rates. However, little is understood about how these cancers develop and outcome remains poor for most patients. Recent studies show that the hormone prostaglandin (PG) plays an important role in liver cancer development and growth. Dr. Chang’s research is examining a receptor called EPI, which plays a role in prostaglandin metabolism. He will test several agents on EPI to determine what effect they have on the growth of liver cancer cells in mice, and on human liver cancer cells. Results from the study may provide important information about the chemoprevention and treatment of human liver cancers.

Daniel Rodriguez, Ph.D.

Institution: The Trustees of the University of Pennsylvania

Each day an estimated 4000 teens try their first cigarette, and more than 2000 adolescents a day become regular smokers. One third of them will die  prematurely from a smoking related disease, such as lung cancer. Physical activity may protect adolescents from beginning to smoke and improve eating habits, as well as overall health. In this study, Dr. Rodriguez is recruiting 350 high school students who will complete two surveys one year apart. The study will measure physical activity, smoking, the students’ physical self-concept, sport competence  beliefs and physical activity enjoyment. The results of this study may help us improve smoking prevention initiatives targeted to teenagers.

2005 Spring Awardees

The CRPF Board of Directors voted to fund ten new grants and fellowships in June, providing $700,000 in support to researchers at nine medical centers in the United States. The investigations include research in the early detection and prevention of lung, breast, prostate, oral, stomach and colon cancer.

Deborah Marshall, Ph.D., MHSA

Institution: McMaster University

CT-scans are today regarded as the most promising technology for the early detection of lung cancer, which has been hard to detect early and is frequently fatal.  Despite recent research about the effectiveness of this tool, we don’t yet know if widespread use of the technique will result in reducing the number of people who die each year from lung cancer.  Dr. Marshall hopes to develop a model for the use of early lung cancer detection. This will help health care policymakers and clinicians better understand the clinical and economic implications of different approaches to lung cancer screening. The overall goal is to provide guidance on the use of CT as a screening tool based on the best evidence and analytical methods available.

Alvin Wee, D.D.S., M.S.

Mentor: Barbara Andersen, Ph.D.
Institution: The Ohio State University Research Foundation

Oral cancer is the sixth most common cancer worldwide and is frequently diagnosed at a late stage when survival rates are poor. Drs. Wee and Andersen hope to increase survival rates through screening for earlier diagnosis.  They are studying groups of patients diagnosed with oral cancer — one group who received late diagnoses and one group whose cancer was diagnosed early. Through interviews, the researchers will examine the patients’ psychological and socioeconomic status, risk/health behavior factors, understanding of symptoms and their access to health care services.  Analysis of this information may help identify variables that relate to when a person is diagnosed.  This information can be used in public awareness campaigns and education of health care professionals to help identify and screen individuals who may be at risk for developing oral cancer.

Sujit Basu, M.D., Ph.D.

Institution: Mayo Clinic Rochester

Approximately 22,000 new cases of stomach cancer were estimated to be diagnosed in 2005 — and nearly half of those diagnosed will die from the disease.  It is often diagnosed in later stages and there are few effective treatments.  Identifying people at a high risk for stomach cancer would greatly help to reduce these sad statistics. Dr. Basu is studying the role of dopamine in the prevention of stomach cancer. His previous research showed that dopamine isn’t present in stomach cancer tissue and treatment with dopamine retards the growth of a human stomach cancer grown in nude mice.  In this phase of research, Dr. Basu hopes to clarify dopamine’s relationship with the pre-cancerous stages of stomach cancer and better understand how it may inhibit the development of the disease — knowledge that may help identify high risk individuals.

Caroline Craig, Ph.D.

Institution: The Regents of the University of California, San Diego

Tobacco use is the leading preventable cause of disease and premature death in the United States.  Despite the fact that smoking and cancer risk have been linked for more than fifty years, fewer than two percent of smokers quit each year, largely because nicotine is addictive. We know that repeated exposure to nicotine causes long-term changes in the brain, but we don’t yet know how this happens. In this study, researchers are examining genes which govern changes in brain cell activity during the development of addiction. They hope to offer insights into the process of nicotine addiction, which may ultimately lead to better interventions for tobacco users.

Yuliya Dobrydneva, Ph.D.

Institution: Eastern Virginia Medical School

Tamoxifen is the most widely used drug for prevention of breast cancer. However, women taking tamoxifen have a high risk for thrombosis, especially deep vein thrombosis, which can be severe and life-threatening. Although it affects millions of women, the reason for the higher occurrence of thrombosis has not yet been established. In this research, Dr. Dobrydneva is investigating the cellular mechanism of tamoxifen-induced thrombosis. Preliminary data suggest that tamoxifen activates calcium and formation of blood clots.  Dr. Dobrydneva is hoping to better understand how and why this occurs — and develop ways to prevent it.

Ruben Gonzalez, Ph.D.

Institution: Boston Biomedical Research Institute

Increased levels of leptin (a human protein related to obesity and reproduction) occur in women who are obese and those who are experiencing menopause. It increases the risk for developing breast cancer and metastasis, as well as lowers survival. There is evidence that indicates that breast cancer may be prevented by blocking the action of the protein.  In this research, Dr. Gonzalez  is testing compounds called Leptin Peptide Antagonists (LPAs) to inhibit leptin, as well as the development of mammary cancer cells in cultures. This is the first time leptin has been targeted for breast cancer prevention. The investigation could generate novel ways to prevent breast cancer, especially in obese and menopausal women.

Milind Suraokar, Ph.D.

Mentor: David Menter, Ph.D.
Institution: University of Texas M.D. Anderson Cancer Center

Drs. Suraokar and Menter are researching the role of dietary fat intake in the prevention of prostate cancer. They are combining biotechnology with bioluminescent to determine the role of fat metabolism in the disease.  Using an innovative technique that harnesses molecules of the Sea Pansy, a bioluminescent soft coral plant, and RNA molecules, the researchers are studying the effect of fats on the tissue of tumors implanted under the skin of nude mice. The cells that are treated with the luminescence from the Sea Pansy glow brightly enough to be detected by a highly sensitive camera.  This research will help us better understand the role of dietary fat in prostate cancer — information that may lead to prevention strategies.

Janet Thomas, Ph.D.

Institution: University of Kansas Medical Center Research Institute, Inc.

Dr. Thomas is investigating an innovative approach to reducing in-home environmental tobacco smoke and motivating smokers to quit. She is recruiting adult nonsmokers who live with smokers and training them to promote smoking behavior change. The project is being conducted with urban, African Americans — an underserved group at high risk for tobacco-related cancer death. The non-smokers will be enrolled in focus groups and results from these discussions will help in the development of a training program. Two different techniques of support will be compared and findings from this initial study will be used to design a larger future investigation.

Larry Dent, Pharm.D.

Institution: The University of Montana

Dr. Dent is conducting the first randomized controlled trial testing the effectiveness of pharmacists in conducting smoking cessation programs. Smokers referred by physicians to one Veterans Health Administration outpatient clinic will be randomly assigned to one of two programs. One will be led by a pharmacist and include three group sessions delivered over five weeks, and the other will consist of one to three, five minute sessions to include all the components of a standard, but brief, clinical intervention. Participants in both programs will receive one medication of their choice (nicotine patch or bupropion) at no-cost.

Ultimately, Dr. Dent envisions that the intervention, if effective, could be disseminated to many of the 200,000 pharmacists in the U.S., including the 5,400 pharmacists in the Veterans Health Administration system.

2004 Fall Awardees

The Cancer Research and Prevention Foundation funded six research grants and/or fellowships in its latest round of support, providing nearly one-half million dollars to promising researchers nationwide.

Ann-Marie Simeone

Institution: M.D. Anderson Cancer Center, University of Texas

Almost half of women diagnosed with breast cancer after menopause are obese. These women also have a higher risk of developing secondary breast malignancies even after chemotherapy and mastectomy.  Simeone is hoping to find an effective way to prevent these secondary cancers and reduce the death rate in these women. She believes that higher levels of the hormones prostaglandin E2 and leptin decrease these patients’ sensitivity to chemopreventive drugs, including the drug Tamoxifen.   Simeone hopes to discover why this happens — information that will help in the development of more effective, tailored chemopreventive strategies that would benefit obese breast cancer patients and improve their clinical outcome.

Vadim Backman, Ph.D.

Fellow:  Young L. Kim, Ph.D.
Institution: Northwestern University

Colon cancer is curable if detected early. And because it grows slowly over time, it can be diagnosed at an early stage. Drs. Backman and Kim are examining a way to use the “field effect” to predict pre-cancerous changes. The field effect refers to the fact that the entire colon changes when a localized tumor in the colon forms.  Identification of early field changes in normal appearing pre-cancerous tissue is important in identifying people at high risk for colorectal cancer. These researchers have developed a technique called “light scattering fingerprinting” that uses a fiber optic probe sensitive enough to visualize even minor changes in colon tissue. They will test the technique in rats and hope to create a simple marker system of tissue changes that may signal cancer risk. The technique could easily be used by primary care physicians during a patient’s annual physical exams.

Swati Nagar, Ph.D

Institution: Temple University

PhIP is a cancer causing compound commonly found in well-cooked meat, which has been  shown to increase colorectal and breast cancer risk. The body contains enzymes that help make the compound less toxic, but their effectiveness varies in one person from the next, depending on an individual’s genetic make-up. Dr. Nagar is studying these genetic differences in hopes of better understanding genetic differences and cancer risk — information that may help improve the effectiveness of chemopreventives in the body.

James M. Ford, M.D.

Fellow:  Allison W. Kurian, M.D.
Institution: Stanford University

New evidence suggests that statins, drugs used to treat high cholesterol, might also prevent breast cancer. In this study, Drs. Ford and Kurian are testing the value of one statin called fluvastatin.  Women with a high genetic risk for the disease will receive the drug over a six-month period.  Then needle biopsies will be performed to see if the drug decreases the proportion of women with abnormal breast duct cells and whether it can decrease other markers associated with breast cancer risk, including breast appearance on imaging tests, and how breast cells grow and repair themselves.

Alfonso Bellacosa, M.D.

Institution: Fox Chase Cancer Center

Colorectal cancer (CRC) is easily prevented if detected early, but better, more cost effective ways to detect the disease are needed. CRC develops over time as benign growths, called polyps, turn into malignant tumors. This is the result of genetic mutation of cells.  Dr. Bellascosa is working to develop a way to identify these early genetic changes in colon tissue using a technology called “microarray analysis,” which maps out the genetic makeup of the genes. With this type of information,scientists may be able to develop specific drugs or diets to prevent the development of polyps — and of colorectal cancer.

Robert J. Korst, M.D.

Institution: Weill Medical College of Cornell University

Lung cancer remains the number one cancer killer in the nation. Surgery is the best treatment choice, but many patients will develop a new lung cancer after their procedure.  Called second primary lung cancer (SPLC), risk for this malignancy increases over time.  CT-scans of the chest can be used after surgery to screen for SPLC.  Dr. Korst is examining this test to determine if it is an cost-effective and useful screening tool and whether the CT-scan is a better test than plain chest x-ray for the early detection of SPLC — results that may help increase lung cancer patients’ chance for survival.

2004 Spring Awardees

The Cancer Research and Prevention Foundation funded six research grants and/or fellowships in its latest round of support, providing nearly one-half million dollars to promising researchers nationwide.

Ann-Marie Simeone

Institution: M.D. Anderson Cancer Center, University of Texas

Almost half of women diagnosed with breast cancer after menopause are obese. These women also have a higher risk of developing secondary breast malignancies even after chemotherapy and mastectomy.  Simeone is hoping to find an effective way to prevent these secondary cancers and reduce the death rate in these women. She believes that higher levels of the hormones prostaglandin E2 and leptin decrease these patients’ sensitivity to chemopreventive drugs, including the drug Tamoxifen.   Simeone hopes to discover why this happens — information that will help in the development of more effective, tailored chemopreventive strategies that would benefit obese breast cancer patients and improve their clinical outcome.

Young L. Kim, Ph.D.

Institution: Northwestern University

Colon cancer is curable if detected early. And because it grows slowly over time, it can be diagnosed at an early stage. Drs. Backman and Kim are examining a way to use the “field effect” to predict pre-cancerous changes. The field effect refers to the fact that the entire colon changes when a localized tumor in the colon forms.  Identification of early field changes in normal appearing pre-cancerous tissue is important in identifying people at high risk for colorectal cancer. These researchers have developed a technique called “light scattering fingerprinting” that uses a fiber optic probe sensitive enough to visualize even minor changes in colon tissue. They will test the technique in rats and hope to create a simple marker system of tissue changes that may signal cancer risk. The technique could easily be used by primary care physicians during a patient’s annual physical exams.

Swati Nagar, Ph.D

Institution: Temple University

PhIP is a cancer causing compound commonly found in well-cooked meat, which has been  shown to increase colorectal and breast cancer risk. The body contains enzymes that help make the compound less toxic, but their effectiveness varies in one person from the next, depending on an individual’s genetic make-up. Dr. Nagar is studying these genetic differences in hopes of better understanding genetic differences and cancer risk — information that may help improve the effectiveness of chemopreventives in the body.

James M. Ford, M.D.

Fellow:  Allison W. Kurian, M.D.
Institution: Stanford University

New evidence suggests that statins, drugs used to treat high cholesterol, might also prevent breast cancer. In this study, Drs. Ford and Kurian are testing the value of one statin called fluvastatin.  Women with a high genetic risk for the disease will receive the drug over a six-month period.  Then needle biopsies will be performed to see if the drug decreases the proportion of women with abnormal breast duct cells and whether it can decrease other markers associated with breast cancer risk, including breast appearance on imaging tests, and how breast cells grow and repair themselves.

Alfonso Bellacosa, M.D.

Institution: Fox Chase Cancer Center

Colorectal cancer (CRC) is easily prevented if detected early, but better, more cost effective ways to detect the disease are needed. CRC develops over time as benign growths, called polyps, turn into malignant tumors. This is the result of genetic mutation of cells.  Dr. Bellascosa is working to develop a way to identify these early genetic changes in colon tissue using a technology called “microarray analysis,” which maps out the genetic makeup of the genes. With this type of information,scientists may be able to develop specific drugs or diets to prevent the development of polyps — and of colorectal cancer.

Robert J. Korst, M.D.

Institution: Weill Medical College of Cornell University

Lung cancer remains the number one cancer killer in the nation. Surgery is the best treatment choice, but many patients will develop a new lung cancer after their procedure.  Called second primary lung cancer (SPLC), risk for this malignancy increases over time.  CT-scans of the chest can be used after surgery to screen for SPLC.  Dr. Korst is examining this test to determine if it is an cost-effective and useful screening tool and whether the CT-scan is a better test than plain chest x-ray for the early detection of SPLC — results that may help increase lung cancer patients’ chance for survival.