Patient Derived Xenograft (PDX) Development and Trial Centers (PDTCs) Network (U54 Clinical Trial Not Allowed) | RFA CA 22 012

Opportunity Information: Apply for RFA CA 22 012

The Patient Derived Xenograft (PDX) Development and Trial Centers (PDTCs) Network funding opportunity (RFA-CA-22-012) is a National Cancer Institute (NCI), National Institutes of Health (NIH) cooperative agreement (U54) designed to build and operate a coordinated set of laboratory-based centers that collectively function as the PDX Development and Trial Centers Research Network, also known as PDXNet. The central idea is to scale up how patient-derived models, especially patient-derived xenografts (tumors implanted and grown in mice), are created, molecularly characterized, and then used in rigorous preclinical testing so that results more reliably inform precision oncology decisions and accelerate therapeutic development. The FOA is explicitly labeled "Clinical Trial Not Allowed," meaning the supported work is preclinical and laboratory-focused rather than involving prospective interventional studies in human participants.

At the core of the program is a push for mechanism-based preclinical trials, particularly for rational drug combinations tested across large panels of molecularly annotated PDX models. These studies are intended to move beyond small, one-off experiments and instead generate stronger, more generalizable evidence about which targeted agents and combinations are most likely to produce meaningful tumor responses in defined molecular contexts. A notable emphasis is placed on NCI-IND agents, meaning investigational drugs for which the NCI holds or supports an Investigational New Drug application, reflecting a priority to advance agents that can plausibly transition from preclinical evidence into early-phase clinical evaluation.

A second major goal is translational decision support: PDTCs are expected to produce evidence-based recommendations for early-phase clinical trials that will be run in NCI clinical trial networks. In practice, that means identifying combinations that generate in vivo evidence of deep and durable responses in PDXs, then packaging those results in a way that is useful for clinical trial design decisions such as which agent pairs to prioritize, which biomarker-defined patient populations may benefit, and what resistance patterns or response durability signals might matter. The program is structured to create a stronger bridge between preclinical findings and the choice of regimens that deserve scarce early-phase trial slots.

Another core responsibility is model development and sharing. Awardees are expected to develop, expand, and characterize new PDX models and contribute them to the NCI Patient Derived Models Repository (PDMR), specifically targeting gaps in the existing national collection. The FOA highlights several high-priority gap areas: models derived from patients with clinical drug resistance (so that relapse and refractory disease biology is represented), models from racial and ethnic minority populations (to improve representation and relevance), and models of rare cancers (where limited commercial incentives often result in sparse model availability). This emphasis reflects the program's intent to make the national PDX resource more comprehensive and equitable, so that preclinical testing does not systematically overlook populations or diseases that are underrepresented in research.

Because preclinical response studies can vary widely in methods and interpretation, PDTCs are also expected to collaborate as a network to develop and apply shared metrics for evaluating in vivo drug response. This part of the FOA is about improving reproducibility and predictive value: creating response measures, experimental standards, and analytical approaches that make PDX response data more comparable across sites and more informative about potential clinical outcomes. Instead of each center using its own endpoints and definitions, the network is expected to converge on approaches that improve confidence in cross-study comparisons and strengthen the credibility of preclinical recommendations.

The opportunity also explicitly addresses cancer outcome disparities. PDTCs are expected to advance understanding of therapeutic outcome differences by race and ethnicity so that early-phase clinical trials are better positioned to support diverse and equitable recruitment. In practical terms, this connects to both model development (ensuring PDX collections include tumors from diverse groups) and data interpretation (examining whether response patterns differ and how that might influence trial eligibility criteria, biomarker strategies, and recruitment planning). The intent is to avoid a pipeline where preclinical evidence is generated primarily from non-representative samples and then translated into trials that unintentionally perpetuate inequities.

Finally, the FOA places strong weight on data sharing and broad utility. PDTCs must devise procedures and platforms to make preclinical PDX data widely accessible to the broader cancer research community, using standards mutually agreed upon by the PDTCs and NCI. This implies structured data generation, consistent metadata and annotation, and dissemination practices that allow outside researchers to interpret, reuse, and build upon PDXNet results, rather than leaving findings locked in isolated institutional systems. In a cooperative agreement mechanism, NCI typically has substantial programmatic involvement, and the network model here underscores coordinated planning, harmonized practices, and shared outputs rather than independent projects operating in parallel.

From an administrative standpoint, the opportunity is a discretionary NIH funding program using a cooperative agreement (U54) mechanism, with activity areas spanning education and health and associated CFDA numbers 93.394 and 93.395. Eligibility is broad across U.S.-based organizations, including state and local governments, public and private higher education institutions, nonprofits (with and without 501(c)(3) status), for-profit entities (including small businesses), independent school districts, special district governments, public housing authorities/Indian housing authorities, and eligible tribal entities. The FOA explicitly lists additional eligible applicant types such as Historically Black Colleges and Universities, Hispanic-serving Institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions, as well as faith-based or community-based organizations and eligible federal agencies. Non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply, and non-domestic components of U.S. organizations are also not eligible; however, foreign components as defined under the NIH Grants Policy Statement are allowed, which typically means limited, well-justified foreign involvement can be included under a U.S. applicant institution when compliant with NIH policy. The original closing date listed for this FOA was 2022-11-01, and the agency is the NIH (with NCI as the sponsoring institute).

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Patient Derived Xenograft (PDX) Development and Trial Centers (PDTCs) Network (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): 93.394, 93.395.
• This funding opportunity was created on 2022-03-25.
• Applicants must submit their applications by 2022-11-01. (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 22 012

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