NCI Posts New “Provocative Questions”

The NCI has earmarked another $40 million over the next 2 years for its Provocative Questions (PQ) Initiative, aimed at funding neglected or understudied areas of cancer research that relate to gaps in current knowledge or address unresolved questions.

The agency has extended the application window from 1 to 2 years and winnowed the list of questions down to 12 from the more than 20 in the three previous Requests for Applications (RFA) issuances published since 2011, says Emily Greenspan, PhD, PQ program director in the NCI's Center for Strategic Scientific Initiatives. The latest RFA specifies four possible deadlines: June 29 and October 29 of this year, and June 29 and October 28 in 2016. Details are available at http://provocativequestions.nci.nih.gov.

“We've learned that the longer period of time is important to give applicants time to carefully consider their applications rather than trying to fit what they're already doing into one of the questions,” says Greenspan. “Our hope is that they will now have time to put together an entirely new application.”

The NCI intends to commit $15 million per year to fund 30 to 40 R01 awards for well-developed projects, and another $5 million per year to fund 15 to 20 R21 awards for exploratory or developmental projects in fiscal years 2016 and 2017. Project periods cannot exceed 5 years for R01 awards and 2 years for R21 awards.

The PQs are not intended to represent the full range of priorities in cancer research but to highlight important areas that may not have received sufficient attention, says Greenspan. To create the new list of questions, the NCI held a series of workshops last fall to get input from the extramural scientific community. Seven questions grew out of those sessions, while the other five were carried over from previous years.

“The questions span the whole gamut of cancer research, from prevention, prognosis, and treatment to health disparities and clinical effectiveness,” says Greenspan. “They are specific but lend themselves to a variety of approaches.”

Successful applicants from previous years have already published some results related to individual PQs. For example, a team funded in 2011 and led by Maja Oktay, MD, PhD, at the Albert Einstein College of Medicine in New York, NY, addressed the PQ, “Given the difficulty of studying metastasis, can we develop new approaches, such as engineered tissue grafts, to investigate the biology of tumor spread?”

Oktay developed an approach to study the invasion of cancer cells into blood vessels, or intravasation, which includes an intravasation assay, optimized isolation of cancer cells from patient samples, and multiphoton imaging to explore cellular interactions that lead to intravasation. Her studies show that intravasation can be prevented in human breast cancer by blocking signaling between cancer cells and macrophages. The findings lay a foundation for developing therapeutic targets to prevent metastasis of multiple breast cancer subtypes (Sci Signal 2014;7:ra112).

Another study funded in 2011 relating to the PQ “How does obesity contribute to cancer risk?” investigated whether dietary fat can be directly taken up by cancer cells to be remodeled into complex lipids which can, in turn, stimulate cancer malignancy and fuel tumorigenicity. Research led by Daniel Nomura, PhD, at the University of California, Berkeley, led to findings suggesting a novel mode of glycolytic control in cancer cells that may promote key oncogenic lipid signaling pathways that drive cancer (ACS Chem Biol 2014;9:1340–50).

“Some of the researchers are producing data that is directly in line with what the PQs are getting at,” says Greenspan. “That's important because these questions are areas where we know there are gaps in our research portfolio.”

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