The Interplay of Cell Death Pathways in Cancer Cell Survival and Resistance to Therapy (R01) | PA 17 440

Opportunity Information: Apply for PA 17 440

The National Institutes of Health (NIH) funding opportunity announcement PA 17-440, titled "The Interplay of Cell Death Pathways in Cancer Cell Survival and Resistance to Therapy (R01)," supports grant-based research focused on how cancer cells avoid being eliminated by regulated cell death programs, especially in the context of treatment resistance. The central idea behind the opportunity is that regulated cell death acts as a natural defense against cancer: when these pathways function properly, they help prevent malignant cells from surviving, spreading, and ultimately forming metastases. Because escaping cell death is a well-established hallmark of cancer, understanding exactly how tumors disable or reroute these death mechanisms is viewed as a direct path to improving therapeutic outcomes, particularly for cancers that no longer respond to standard drugs.

A key scientific motivation for the FOA is the growing recognition that multiple cell death machineries can coexist within the same cell, including apoptosis and necroptosis. Apoptosis is the classic programmed cell death pathway often targeted by therapies, while necroptosis is a distinct regulated pathway that can serve as an alternative route to kill cells when apoptosis is blocked. Even though the components needed to trigger different death programs may be present, the way these pathways communicate, compensate for one another, or are jointly suppressed in cancer has not been studied in a comprehensive or systematic way. This FOA is intended to push the field toward studying that "crosstalk" rather than examining each pathway in isolation, with an emphasis on both treatment-naive tumors and tumors that have already developed drug resistance.

The opportunity highlights practical translational payoffs from this line of research. By mapping the intersection of cell death programs at a molecular level, researchers may be able to define clearer, more reliable biomarkers that indicate which death pathway is engaged, blocked, or rewired in a given tumor setting. Those markers could then guide therapy choices or patient stratification. In addition, the FOA explicitly points to therapeutic strategies that could emerge from mechanistic insights, such as inhibiting specific mediators that support cancer cell survival or, conversely, enhancing mediators that push cells toward apoptosis, necroptosis, or other regulated death outcomes. The overarching goal is to identify vulnerabilities that can be exploited to force both untreated and drug-resistant cancer cells into effective cell death, thereby reducing progression, metastasis, and therapeutic failure.

Administratively, this is a discretionary NIH grant opportunity using the R01 mechanism, and it falls under the education and health activity category (CFDA 93.396). Eligibility is broad and includes many types of U.S. organizations and governments, such as state, county, city, township, and special district governments; federally recognized Native American tribal governments; public and state-controlled institutions of higher education; private institutions of higher education; independent school districts; and public or Indian housing authorities. The FOA also allows applications from nonprofits (with or without 501(c)(3) status), for-profit organizations (other than small businesses), and small businesses, reflecting an intent to encourage participation from a wide range of research-performing entities.

The announcement also specifically names additional eligible applicant categories to promote inclusivity and reach, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs (Asian American Native American Pacific Islander Serving Institutions), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), tribal governments that are not federally recognized, faith-based or community-based organizations, U.S. territories or possessions, regional organizations, eligible federal agencies, and non-U.S. entities (foreign organizations). The FOA was created on 2017-08-04, and the original closing date listed is 2020-09-07. Award ceiling and expected awards are not specified in the provided source data, which typically means applicants would need to consult the full FOA text or NIH budget guidance for the most current funding and award expectation details.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "The Interplay of Cell Death Pathways in Cancer Cell Survival and Resistance to Therapy (R01)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.396.
• This funding opportunity was created on 2017-08-04.
• Applicants must submit their applications by 2020-09-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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