Research Highlights - Archives FY11
Seed Funding Research Program Grant Awards
We congratulate the six investigators who received awards this round.
Pilot test of a lifestyle intervention arm in an endometrial cancer prevention trial: Effects on endometrial proliferation and related biomarkers
Women who are obese and have low levels of physical activity are more likely to develop endometrial cancer (cancer of the lining of the uterus), but we do not yet know if losing weight and becoming more active will decrease a woman’s risk of this disease. The goal of our research is to answer this question.
We are collaborating with investigators from MD Anderson’s SPORE (Specialized Program for Research Excellence) in uterine cancer who are doing a trial to test whether metformin, a drug usually used to treat diabetes, can help reduce cell growth in the endometrium of women who are obese. We will add another arm to this trial in which the participants will receive a diet and exercise program to help them lose weight. All women participating in the SPORE study will have endometrial biopsies to assess cell growth as well as blood tests to measure markers that may be related to the risk of developing endometrial cancer. This pilot study will help us determine whether there is enough evidence to show that changing diet and exercise behavior affect s endometrial cancer risk and, if so, justify doing a larger clinical trial.
A feasibility study for high-throughput application of a novel early detection and risk assessment biomarker
In this study, we will test the feasibility of automating a biomarker that comprehensively allows the measurement of cellular genomic instability. We have shown that cytokinesis blocked micronucleus assay is a sensitive predictor of lung cancer risk. Automation of this powerful assay will provide a strong, rapid and unbiased quantitative analysis tool for cancer risk assessment. We envision using this biomarker in lung cancer screening programs as a prescreening tool for current and former smokers prior to CT screening. This prescreen will allow the identification of individuals at high risk of development of lung cancer, and who therefore warrant further screening and follow-up using CT. Given the low cost, accuracy and safety, this biomarker test could be potentially valuable for screening of large populations.
Identifying neurocognitive risk markers that differentiate smokers from never-smokers and ex-smokers
Even though most smokers know that smoking is unhealthy, and despite most wanting to quit, only 6% of those who make a serious quit attempt are still abstinent one year later. The problem is that smoking, like other drugs of abuse, alters the brain after repeated use, alterations that make it difficult to quit and to stay abstinent. We want to examine whether brain markers that we previously identified in smokers exist in never smokers and ex-smokers. The ultimate goals of the grants that will result from this proposal would be to use these brain markers to predict which nonsmokers are at risk from becoming smokers and which ex-smokers are likely to have problems staying abstinent.
Integrative Genomic Analysis of Actinic Keratoses: Using Inter-lesional and Cross Species Analysis to Predict Progression to Cutaneous Squamous Cell Carcinoma
Skin cancer is the most common malignancy in humans, of which there are over 3 million cases a year in the United States, costing an estimated $500 million in treatment-related costs and $2 billion in overall economic impact. Cutaneous squamous cell carcinoma (the 2nd most common skin cancer) has a well-ordered sequence of development beginning with chronically sun-exposed skin, progressing to the most common precancerous lesion in humans, the actinic keratosis (AK), and then ultimately to invasive cancer. The tremendously high incidence of AK presents a vast opportunity for secondary skin cancer prevention, and our proposed studies to identify the important genetic alterations that result in AK formation will enable the design of better interventions to eliminate them and prevent their progression to cancer.
High Throughput Search for a Combination Cancer Preventive Treatment
The two most fundamental criteria for the development of cancer preventive agents are achieving high effectiveness and low toxicities associated with chemopreventive medication, typically administered over a long period of time. The proposed research addresses both issues. Its goal is to identify drug combinations which more effectively suppress cell growth and prevent cancer than either individual component alone. At the same time this research will develop new treatment options that reduce the effective dosage by combining cancer preventive agents to achieve equivalent or synergistic effects. Achieving these goals may have a tremendous impact on the acceptance of pharmacologic preventive strategies.
Chemoprevention of pancreatic cancer by induction of synthetic lethality in mutant K-ras cells
Pancreatic cancer is often diagnosed at an advanced stage and has a poor prognosis. Activating mutations of the K-ras oncogene are possibly the single most common genetic abnormality in pancreatic cancer. Therefore, mutant K-ras gene or its gene product represents an obvious target for the treatment and prevention of pancreatic cancer. In this application, we propose to develop a novel method to specifically abolish oncogenic K-ras expressing cells for pancreatic cancer prevention and treatment.
2011 Cancer Survivorship Research Seed Grants
Congratulations to the winners:
Health status and health behaviors among cancer survivors: a population-based study
Little data exists regarding the health status and experiences of cancer survivors, particularly for survivors of the less common cancers and of racial and ethnic minority populations. The Behavioral Risk Factor Surveillance System (BRFSS) is an annual telephone survey conducted by the Centers for Disease Control (CDC) that collects data regarding various health conditions and risk behaviors in the U.S. population. We propose to use data from the 2009 and 2010 BRFSS surveys regarding health problems and behaviors in cancer survivors to identify subgroups of survivors who are likely to benefit from interventions based on their needs. Using these data, we will estimate the prevalence of certain health problems and health behaviors in cancer survivors and in a group of control individuals without cancer. We will also examine differences in the prevalence of these health conditions and behaviors among various subgroups of the survivor population. This work will provide estimates of the public health significance of cancer survivorship issues within the U.S. Such estimates are critical to the design of future intervention studies, guidelines and collaborative care models for cancer survivors.
Toward an understanding of body image adaptation following surgical treatment for head and neck cancer.
Body image is recognized as a critical psychosocial issue for individuals with head and neck cancer. The purpose of this study is to determine how such patients make sense of their appearance and body image changes after surgery. We will conduct interviews with 20 patients and 15 healthcare providers. Our primary research questions involve examining the immediate emotional reactions and psychosocial ramifications of mirror-viewing during the acute postoperative phase, as well as developing an understanding of how these may change throughout the course of active treatment and into the period of survivorship. There will be a specific focus on obtaining data regarding current standards of care for assisting patients with mirror-viewing during and following treatment. The proposed work is anticipated to enhance knowledge regarding fundamental body image issues for the head and neck cancer patient population and can be used to guide future studies and the development of novel psychosocial interventions for this patient population.
The role of tryptophan metabolism in the chronic fatigue experienced by chronic myelogenous leukemia (CML) survivors
In order to avoid recurrence, survivors of chronic myelogenous leukemia (CML) must remain on tyrosine kinase inhibitor (TKI) therapy for years, if not for the remainder of their lives. Fatigue is recognized as one of the most common complications of this long-term therapy. The mechanism of this TKI-induced fatigue is currently unknown; however, recent studies suggest tryptophan degradation may play a role. Based on these studies, we propose an in-depth longitudinal study to track the temporal patterns of tryptophan degradation and its association with fatigue and QoL in CML survivors. We will measure the degree of association between tryptophan degradation and the incidence of fatigue as well as changes in QoL over time in CML survivors undergoing TKI therapy. We will also examine the impact of various CML treatments on such associations as well as assess which TKI maintenance therapy may be more suitable for older CML survivors based on their temporal patterns of tryptophan degradation, fatigue and QoL.
Impact of past chemotherapy on emotional processing: an fMRI study in breast cancer survivors
More than half of breast-cancer survivors suffer from loss of sexual desire, particularly if they have had chemotherapy. This loss does not appear to correlate with serum androgen levels and pharmaceutical and sex therapy treatments have not had more than modest success in treating this loss of desire. Our hypothesis is that chemotherapy does long-term damage to the neural networks in the brain necessary for emotional processes. We will use functional magnetic resonance imaging (fMRI) in a pilot study of breast cancer survivors 40-60 years of age to measure brain activity while viewing standardized sets of pleasant, unpleasant and neutral pictures. Results of this study will lead to further research on the impact of chemotherapy on the brain’s emotional pathways and contribute to the design of future studies aimed at developing more effective remedies for the frequent problem of long-term loss of sexual desire in breast cancer survivors.
A brain-plasticity based computerized intervention to treat attention and memory problems in adult brain tumor survivors
Survival times have improved for individuals with brain tumors (BT), however, the majority of BT survivors suffer from cognitive impairment associated with reduced independence, decreased ability to participate in daily living activities, and increased caregiver distress. Rehabilitation in the form of compensatory training requiring intensive in-person therapy lasting weeks to months and involving multi-disciplinary teams of care providers is available to some, but not all, BT survivors due to geographic and financial reasons. The Brain Fitness Program (Posit Science, San Francisco, CA) is an at-home, web-accessible brain plasticity-based computerized intervention for improving cognitive function in the elderly that may be applicable to BT survivors. The goal of this proposal is to determine the feasibility and acceptability of the Brain Fitness Program in BT survivors, as measured by improvement in a directly trained measure from the Brain Fitness Program among BT survivors, as well as by changes in self-reported everyday cognitive function and in objective neuropsychological tests of attention and memory. These results will build the basis for developing and powering larger clinical trials to determine the efficacy and effectiveness of this broadly available intervention.
Seed Funding Research Program Grant Awards
We congratulate the two investigators who received awards this round.
Germline genetic variants in the Wnt/beta-catenin stem cell pathway as predictors of colorectal cancer risk
Colorectal cancer is the 3rd most common malignancy with nearly 150,000 new cases diagnosed each year in the United States. These studies will shed light on the effect of common, germline genetic variation within the Wnt/beta-catenin stem-cell signaling pathway on colorectal cancer risk. The results can contribute to a personalized risk prediction model that will help to understand an individual’s risk of colorectal cancer development and provide recommendations of suitable prevention strategies with the goal of reducing the incidence and burden of this deadly disease.
Glioma susceptibility in African American and Hispanic Populations
Gliomas, the most common type of brain tumors, have very poor prognosis and are associated with considerable morbidity and mortality. Investigators have long known that gliomas are more common in Caucasians than in African Americans and Hispanic Americans. The proposed research focuses on discovering genetic markers among African Americans and Hispanic Americans populations. This research will help explain why glioma affects Caucasians more often than African Americans and Hispanic Americans, and will potentially lead to new and improved modes of diagnosis and prevention for patients with glioma.
Seed Funding Research Program Grant Awards
We congratulate the two investigators who received awards this round.
Pilot Biomarker Study of Trace Metals and Prostate Cancer Risk
The purpose of this research study is to investigate the role of essential and toxic trace metals and their association with prostate cancer among African American and white men. Researchers in Dr. Hoque’s laboratory will measure levels of essential and toxic metals in blood among both prostate cancer patients and healthy men to determine if there is an association of low levels of essential or high levels of toxic metals with prostate cancer. In addition, Dr. Hoque’s group will examine whether certain dietary factors, such as fruit and vegetable consumption and dietary supplements, reduce the toxic effects of heavy metals and ultimately decrease prostate cancer risk. Data generated from this study could have significant public health implications through the identification of a population with deficient essential trace metals that could be at high risk for prostate cancer and, therefore, could benefit from targeted primary and secondary prevention interventions.
Cost-effectiveness Studies of Novel Cancer Prevention Strategies
Many genetic risk factors have been identified for complex human diseases such as lung cancer but it is unclear how to make effective use of such information to improve existing cancer prevention strategies. This study aims to simulate populations with realistic environmental and genetic risk factors of cancers, and then study the cost-effectiveness of novel cancer prevention strategies that make use of individual genetic information. By predicting and comparing the benefits, harms, and costs of various cancer prevention strategies, the results of this project could contribute to development of tools to help clinicians make recommendations regarding the benefits of genetic testing for individuals who are at risk for certain types of cancers, and, ultimately, aid clinicians in providing individualized cancer prevention and treatment options according to a patient’s individual genetic profile.
Mentored Junior Faculty Fellowship
Applications are being accepted for the Duncan Family Institute Mentored Junior Faculty Fellowship in Cancer Prevention Research.
Cancer Prevention and Population Sciences Faculty in the News
- Same cancer, different time zone Paul Scheet, Ph.D.
- End Tobacco: It will take a village to tackle tobacco Ernest Hawk, M.D., M.P.H. and Lewis Foxhall, M.D.
- High-tech 3D mammogram probably saved this woman's life Therese Bevers, M.D.
- Powerful tool combs family genomes to find shared variations causing disease Chad Huff, Ph.D.