Acquired Resistance to Therapy Network (ARTNet; U54 Clinical Trial Not Allowed) | RFA CA 21 052

Opportunity Information: Apply for RFA CA 21 052

The Acquired Resistance to Therapy Network (ARTNet; U54, Clinical Trial Not Allowed) is a National Cancer Institute (NCI) cooperative agreement funding opportunity aimed at building a multi-institutional research network to understand why cancers that initially respond to treatment later become resistant and recur. This FOA is a reissue and refinement of NCI's earlier Drug Resistance and Sensitivity Network (DRSN, RFA-CA-17-009), with a sharper emphasis on the mechanistic basis of acquired resistance across modern cancer therapies and on generating knowledge that can realistically be translated into strategies to prevent, delay, or overcome resistance.

A defining feature of ARTNet is its required "team science" structure. The program is designed to connect basic biology, preclinical modeling, and translational investigation in an iterative way, rather than treating them as separate lanes of work. The scientific focus explicitly spans the tumor-microenvironment continuum, meaning applicants are expected to consider not only tumor cell-intrinsic mechanisms (like pathway rewiring, target alteration, or clonal selection) but also contributions from the surrounding microenvironment (such as immune context, stromal interactions, metabolic constraints, and therapy-induced changes). The underlying intent is to create a cycle where discoveries in mechanistic studies inform model development and translational hypotheses, and where translational observations feed back into deeper mechanistic work, accelerating progress toward intervention concepts that could ultimately be tested in future clinical settings (while not being funded as clinical trials under this FOA).

The award mechanism is a U54 cooperative agreement, which signals substantial NCI involvement in the program's coordination and scientific direction compared with a standard research project grant. In practical terms, ARTNet is meant to function as a network rather than a collection of isolated projects, with expectations around collaboration, shared approaches, and alignment with network-wide goals. This FOA is published in parallel with a companion opportunity for a Coordinating and Data Management Center (CDMC) using the U24 mechanism. The CDMC component is intended to support network-wide coordination and data management so that outputs from participating sites can be harmonized, shared, and leveraged across the consortium. Applicants to the U54 should expect that their work will interface with the CDMC and conform to network standards for data and collaboration.

Eligibility is broad and includes many types of U.S.-based organizations: state, county, and local governments; special district governments; independent school districts; public housing authorities; public and private institutions of higher education; federally recognized Native American tribal governments; other Native American tribal organizations; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses. The FOA also highlights additional eligible applicant categories such as Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions. At the same time, it states that non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components, as defined in the NIH Grants Policy Statement, are allowed, meaning a U.S. applicant organization may include certain foreign activities or collaborations if they meet NIH's definition and requirements for foreign components.

Administratively, the opportunity is run through the National Institutes of Health (NIH) with NCI as the sponsoring institute, and it falls under CFDA numbers 93.395 and 93.396. The funding instrument type is a cooperative agreement, and the activity category is listed under education and health. The original closing date provided in the source data is 2021-11-01, and the opportunity was created on 2021-08-03. The listing does not specify an award ceiling or expected number of awards in the excerpt provided. The "Clinical Trial Not Allowed" designation means applications should not propose independent clinical trials as part of the funded activities; the emphasis is on mechanistic and translational research that prepares the ground for future clinical testing rather than conducting clinical trials within this award.

Overall, ARTNet is positioned as an NCI-supported collaborative infrastructure to tackle one of the biggest barriers to durable cancer control: the near inevitability of therapy resistance in many settings. The program is built to produce integrated mechanistic understanding across tumor biology and the microenvironment, validated through appropriate preclinical and translational work, and organized in a way that prioritizes shared progress across a network rather than stand-alone results from individual labs.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Acquired Resistance to Therapy Network (ARTNet; U54 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.395, 93.396.
• This funding opportunity was created on 2021-08-03.
• Applicants must submit their applications by 2021-11-01. (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.

Apply for RFA CA 21 052

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