Unlike most FOAs, the PQ solicitation does not list “examples” of research topics … you will address one (and only one) PQ per application submitted:
Each application must address one and only one specific PQ, exactly as defined in this FOA. … They should NOT be construed as “examples” of specific topics. The scientific scope of each individual application must clearly and distinctly correspond to one (and only one) of the PQs listed above. Within an area defined by a given PQ, applicants may propose and pursue any topic they deem relevant as a “research answer” to that PQ. It is essential, however, that applicants visit “Provocative Question” web site (http://provocativequestions.nci.nih.gov/) for additional information for each PQ pertaining to context, background, feasibility, and expectations of needs to be accomplished for a successful solving of these problems.
Note: Applicants who fail to choose a specific PQ from this list, address more than one PQ within a single application, and/or re-write the PQ will have their applications rejected without review as non-responsive.
And without further ado, the questions are:
PQ1. How does obesity contribute to cancer risk?
PQ2. What environmental factors change the risk of various cancers when people move from one geographic region to another?
PQ3. Are there ways to objectively ascertain exposure to cancer risk using modern measurement technologies?
PQ4. Why don’t more people alter behaviors known to increase the risk of cancers?
PQ5. Given the evidence that some drugs commonly and chronically used for other indications, such as an anti-inflammatory drug, can protect against cancer incidence and mortality, can we determine the mechanism by which any of these drugs work?
PQ6. What are the molecular and cellular mechanisms by which patients with certain chronic diseases have increased or decreased risks for developing cancer, and can these connections be exploited to develop novel preventive or therapeutic strategies?
PQ7. How does the life span of an organism affect the molecular mechanisms of cancer development and can we use our deepening knowledge of aging to enhance prevention or treatment of cancer?
PQ8. Why do certain mutational events promote cancer phenotypes in some tissues and not in others?
PQ9. As genomic sequencing methods continue to identify large numbers of novel cancer mutations, how can we identify the mutations in a given tumor that are most critical to the maintenance of its oncogenic phenotype?
PQ10. As we improve methods to identify epigenetic changes that occur during tumor development, can we develop approaches to discriminate between “driver” and “passenger” epigenetic events?
PQ11. How do changes in RNA processing contribute to tumor development?
PQ12. Given the recent discovery of the link between a polyomavirus and Merkel cell cancer, what other cancers are caused by novel infectious agents and what are the mechanisms of tumor induction?
PQ13. Can tumors be detected when they are two to three orders of magnitude smaller than those currently detected with in vivo imaging modalities?
PQ14. Are there definable properties of a non-malignant lesion that predict the likelihood of progression to invasive or metastatic disease?
PQ15. Why do second, independent cancers occur at higher rates in patients who have survived a primary cancer than in a cancer-naïve population?
PQ16. How do we determine the clinical significance of finding cells from a primary tumor at another site?
PQ17. Since current methods to assess potential cancer treatments are cumbersome, expensive, and often inaccurate, can we develop other methods to rapidly test interventions for cancer treatment or prevention?
PQ18. Are there new technologies to inhibit traditionally “undruggable” target molecules, such as transcription factors, that are required for the oncogenic phenotype?
PQ19. Why are some disseminated cancers cured by chemotherapy alone?
PQ20. Given the recent successes in cancer immunotherapy, can biomarkers or signatures be identified that can serve as predictors or surrogates of therapeutic efficacy?
PQ21. Given the appearance of resistance in response to cell killing therapies, can we extend survival by using approaches that keep tumors static?
PQ22. Why do many cancer cells die when suddenly deprived of a protein encoded by an oncogene?
PQ23. Can we determine why some tumors evolve to aggressive malignancy after years of indolence?
PQ24. Given the difficulty of studying metastasis, can we develop new approaches, such as engineered tissue grafts, to investigate the biology of tumor spread?
One unspoken PQ: will the payline for these fall at the 7th percentile and/or at Harold’s discretion?