Group A: Cancer Prevention and RiskThere are four questions in this group.
View RFA (R01) | View RFA (R21)
How do decision making processes influence habitual behaviors, and how can that knowledge be used to design strategies that lead to adoption and maintenance of behaviors that reduce cancer risk?
Background: A wealth of epidemiological research shows that certain modifiable and habitual behaviors are linked to increased cancer risk; these include tobacco use, UV exposure and obesity-related behaviors such as overeating and physical inactivity. Despite awareness of the link between these behaviors to the risk of cancer and other diseases, many individuals find it difficult to change those behaviors. Research on basic decision-making processes, emotion, and motivation, could shed light on why people fail to alter behavioral patterns and could inform the development of interventions to increase healthy behaviors and ultimately improve cancer outcomes.
Feasibility: Opportunities exist to leverage methodological perspectives and tools from sciences (e.g., marketing and consumer science, industrial and organizational psychology, neuroscience) far afield of traditional cancer research to understand and change behaviors known to increase cancer risk.
Implications of success: Reduced cancer morbidity and mortality as a result of modified health behaviors associated with disease risk.
How does the level, type, or duration of physical activity influence cancer risk and prognosis?
Background: Several studies have shown that physical activity has important but poorly understood features that lower cancer risk and positively affect the progression of tumor development. These effects are not just due to weight loss or caloric restriction. This Provocative Question seeks studies to determine what features or types of physical activity are most important in achieving these benefits, and what is the mechanism underlying these effects.
Feasibility: Researchers may be able to expand or utilize existing studies or possibly initiate new studies to learn what components of physical activity affect cancer incidence or progression. Among the important features that could be studied are: What types of physical activity, ranging from active life style to aerobic or anaerobic workout programs, lead to these benefits? Is the length of activity or the intensity key to the advantages? What molecular changes induced by physical activity might be linked to the beneficial effects?
Implications of success: Better understanding of how physical activity affects cancer will lead to stronger and better recommendations about healthy life style. Eventual understanding of the molecular causes for such benefits could lead to better understanding of what physiological events could serve as models to future prevention research.
What biological mechanisms influence susceptibility to cancer risk factors at various stages of life?
Background: Cells and tissues in various developmental stages will respond differently to risk exposures. A simple well-known example of differential response is seen for cells in early development, which may be more susceptible to exposures that rely on DNA synthesis than when cells reach adult stages where division is less common. Similarly, exposure risks may be more important when cells are in other stages or under other types of pressures. This Provocative Question seeks experimental approaches that can be used to distinguish when risks are most dangerous and then asks what molecular mechanisms underlie these differences.
Feasibility: Since the measurement of changes induced by risk factor exposure is key to success for this question, it will be essential to identify appropriate systems for study. Starting new longitudinal studies in humans is beyond the scope of this question; therefore, applicants are encouraged to identify other systems where exposure effects can be linked to various outcomes and studied in more detail. Experiments in mice will provide one potential system where both the effect and outcome of exposure can be measured and studied. In addition, some existing human exposure samples may be available for such studies. The goal of these experiments is to move beyond simple observational studies and determine what molecular mechanisms account for the differential responses to risk exposure.
Implications of success: Learning what cellular processes promote and inhibit the effects of exposure will help us understand important variations in the early stages of tumor development. These differences will provide needed insight into how one might identify targets for prevention and early detection. Such information will also help the community prepare better guidance for the management of risk.
For tumors that arise from a pre-malignant field, what properties of cells in this field can be used to design strategies to inhibit the development of future tumors?
Background: Several lines of experimentation have shown cells that surround solid tumors often carry mutations or epigenetic changes characteristic of the tumor itself. These cells appear normal or at least more like normal cells than the tumor, but their genetic or epigenetic changes suggest that they may be derived from the same precursor cell that led to the tumor. This Provocative Question expands on these observations and asks for experimental approaches that might use the changes seen in surrounding cells as potential targets to prevent the appearance of future tumors from these fields.
Feasibility: Investigators will need to identify a useful tumor development model to study these types of changes. These could be in the mouse or there may be specific tumor and nearby non-tumor samples available for some human tissues. Comparisons using omic style studies would be the most likely source for the identification of potential similarities in tumors and surrounding cells but not in more distant normal cells. These then could be used to build and test hypotheses about new targets for treatment or prevention of future tumor development.
Implications of success: The results from these studies will provide a useful tumor development model for the identification of early stage lesions. Comparison of responses with drugs targeting early stage lesions versus late stage lesions will help us understand the importance of choosing among various targets based on their stage of appearance. In addition, such studies might suggest diagnostic steps that could identify early lesions and thus might help prioritize target selection. Similarly it may be possible to design trials to block the development of future tumors based on the identification of the earliest lesions. Finally, the classification of lesions as either early or late promises to help us understand the development pattern of certain tumor mutations.