Research Answers to NCIs Provocative Questions (R01) | Apply Online

Opportunity Summary:

Research Answers to NCI's Provocative Questions (R01) (Funding Opportunity Number RFA-CA-15-008) is a discretionary grant opportunity from the National Institutes of Health, focused through the National Cancer Institute (NCI), that funds investigator-initiated research projects aimed at tackling a targeted set of stubborn, underexplored problems in cancer research. The central idea behind this program is the "Provocative Questions" initiative, where NCI identifies specific puzzles, paradoxes, or gaps in understanding and frames them as direct questions. Applicants are expected to design R01-level research projects that can generate concrete answers to one or more of these questions, often by bringing fresh thinking, unconventional approaches, or new tools to areas that are scientifically important but historically have not attracted enough sustained attention.

The opportunity is intentionally not meant to cover all of NCI's cancer research priorities. Instead, it concentrates funding on a curated list of challenge questions that highlight areas where progress has been slow, where existing assumptions may be limiting, or where contradictory findings suggest that key biology or clinical realities are being missed. In practice, that means proposals should be organized around a clearly defined problem statement that aligns with the Provocative Questions framework and proposes a rigorous plan to resolve it. The expected outcome is more than incremental progress; the program is oriented toward clarifying confusing observations, resolving inconsistencies, or opening up new directions by explaining why something in cancer behaves in an unexpected way.

This announcement uses the R01 grant mechanism, which generally supports substantial, multi-year research projects with a strong scientific premise, a coherent set of aims, and a well-justified strategy for producing interpretable results. While the content of individual projects can vary widely, the common thread is that the work should be responsive to the Provocative Questions initiative and should directly address one of the identified questions in a way that could meaningfully shift understanding or practice in cancer research. The funding activity falls under health and education-related research, and it maps to multiple NCI-related CFDA program areas, including cancer cause and prevention (93.393), detection and diagnosis (93.394), treatment (93.395), biology (93.396), and control (93.399). This reflects how the Provocative Questions can span the full cancer research continuum, from basic mechanisms to clinical and population-level issues.

The estimated total funding associated with this opportunity is $15,000,000, and there is no cost-sharing or matching requirement, which means applicants are not required to contribute non-federal funds as a condition of receiving an award. The FOA was posted and created on March 27, 2015. The original and final closing date listed is October 28, 2016, and the opportunity was archived on November 28, 2016, indicating it is no longer active for new submissions under that specific announcement number and cycle, though similar Provocative Questions initiatives may appear under other, newer solicitations.

Eligibility is broad and includes many types of U.S. organizations as well as non-U.S. entities. Eligible applicants include public and state-controlled institutions of higher education, private institutions of higher education, nonprofit organizations both with and without 501(c)(3) status, small businesses, and other for-profit organizations (including those other than small businesses). Government entities at multiple levels are also eligible, including state governments, county governments, and city or township governments, along with special district governments and independent school districts. The announcement also explicitly includes tribal governments and tribal organizations, such as federally recognized Native American tribal governments as well as other tribal entities, and it extends eligibility to U.S. territories or possessions. In addition, the eligibility language highlights a range of mission-serving institutions and community-connected organizations, including Historically Black Colleges and Universities (HBCUs), Hispanic-Serving Institutions, Tribal Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American, Native American, and Pacific Islander Serving Institutions (AANAPISIs), as well as faith-based or community-based organizations and regional organizations. Importantly, non-domestic (non-U.S.) entities (foreign organizations) are also listed as eligible, which signals that NCI is open to funding strong ideas wherever the expertise is located, provided the application meets NIH requirements.

From an applicant's perspective, the main strategic takeaway is that success depends on convincingly linking the proposed research plan to one of NCI's Provocative Questions and showing how the project will produce a clear, testable, and meaningful answer. A strong application would typically demonstrate why the question matters, why it remains unresolved, what specific barrier has prevented progress, and how the proposed approach breaks through that barrier with solid methods and measurable milestones. Because the questions are designed to be provocative, applications that simply apply routine methods without addressing the underlying paradox or without a compelling logic for why the work will resolve the question may be less competitive than those that directly confront the conceptual challenge.

The official announcement is available through the NIH grants archive at http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-15-008.html. For technical issues accessing or linking to the full announcement, the listed point of contact is the NIH Office of Extramural Research (OER) Webmaster at FBOWebmaster@OD.NIH.GOV.

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