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This initiative has assembled a list of 20 important questions to stimulate the research communities to use laboratory, clinical and population sciences in especially effective and imaginative ways to answer the questions. Funding: RO1 - 4 years, amount unlimited; R21 - $275K over 2 years.
Group A: Cancer Prevention and Risk
A1: 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?
A2: How does the level, type, or duration of physical activity influence cancer risk and prognosis?
A3: What biological mechanisms influence susceptibility to cancer risk factors at various stages of life?
A4: 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?
Group B: Mechanisms of Tumor Development or Recurrence
B1: Why do second, independent cancers occur at higher rates in patients who have survived a primary cancer than in a cancer-naïve population?
B2: What molecular and cellular events in the tumor microenvironment (for example, the local immune response) determine if a tumor at the earliest stages of malignant transformation is eliminated, stimulated for further development, or made indolent?
B3: What mechanisms initiate or sustain cancer cachexia, and can we target them to extend lifespan and quality of life for cancer patients?
B4: What methods can be devised to characterize the functional state of individual cells within a solid tumor?
Group C: Tumor Detection, Diagnosis, and Prognosis
C1: What properties of pre-cancerous lesions or their microenvironment predict the likelihood of progression to malignant disease?
C2: What molecular or cellular events establish tumor dormancy after treatment and what leads to recurrence?
C3: How do variations in tumor-associated immune responses among patients from distinct well-defined populations, such as various racial/ethnic or age groups, contribute to differences in cancer outcomes?
C4: What in vivo imaging methods can be developed to portray the "cytotype" of a tumor — defined as the identity, quantity, and location of each of the different cell types that make up a tumor and its microenvironment?
Group D: Cancer Therapy and Outcomes
D1: What molecular properties make some cancers curable with conventional chemotherapy?
D2: What features of standard-of-care therapies enhance or inhibit the efficacy of immunotherapy?
D3: Do tumors evolve common features that could act as new therapeutic targets when they metastasize to the same secondary site?
D4: What are the mechanistic bases for differences in cancer drug metabolism and toxicity at various stages of life?
Group E: Clinical Effectiveness
E1: What strategies optimize adoption and sustainability of guideline concordant cancer treatments in community settings?
E2: What care delivery models can be developed to transition cancer patients effectively from active therapy to end of life care?
E3: What methods and approaches induce physicians and health systems to abandon ineffective interventions or discourage adoption of unproven interventions?
E4: What are the best methods to identify and stratify subgroups of patients with particular co-morbidities who will benefit from defined cancer therapies?
Key Dates: Application deadline is 20.6. Letter of Intent due 20.5 (is not mandatory, not binding, and does not enter into the applications review, yet it allows IC staff to estimate the potential review workload and plan the review).
http://provocativequestions.nci.nih.gov/ | http://provocativequestions.nci.nih.gov/rfa
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