Patient-Derived Xenograft Development and Trials Center Research Network (PDXNet)

Background

Increasing the effectiveness of cancer therapy requires matching the assignment of treatments to those cancer indications for which they have the best outcome. As more targeted agents become available, and tumor subtypes are further defined, researchers must prioritize and test optimal combinations of agents in increasingly narrow tumor subsets in early phase clinical trials.

New preclinical methods are needed to test novel agents against hundreds of potential tumor subtypes, and in multiple combinations. In this way we may identify the most promising strategies for clinical evaluation. Patient-derived models, such as patient-derived xenografts (PDXs) and patient-derived organoids (PDOs), offer the potential to better represent human tumor biology than established cell lines do. This is due to their low passage number. Therefore, patient-derived models may serve as better predictive models of tumor response to therapeutic approaches.

Formation and Structure of PDXNet

Funded through the 21st Century Cures Act in 2017, NCI granted awards for four U54 teams (PDX Development and Trial Centers [PDTCs] RFA-CA-17-003) and one U24 team (PDXNet Data Commons and Coordinating Center [PDCCC] RFA-CA-17-004). NCI awarded additional administrative supplements (PA-18-496 and PA-19-174) to support the access of non-PDXNet NCI-funded investigators to PDXNet resources.  

In addition, the NCI Center for Cancer Health Care Disparities (CRCHD) administered two additional U54 PDTCs (RFA-CA-17-032) for the use of patient-derived models from racial and ethnic minority populations to explore the biological reasons behind disparate cancer therapy outcomes in these patient populations.  

PDXNet was approved for a second grant cycle that began in September 2023. It continues to be a collaboration between DCTD and CRCHD. NCI granted seven awards in total, six U54 (RFA-CA-22-012) PDTC teams and one U24 (RFA-CA-22-013) PDCCC team. 

PDXNet Goals

The primary objective of PDXNet is to perform large-scale studies that test therapeutic strategies in models that represent the molecular diversity of cancer histologies and clinically validate the experimental results. The network emphasizes testing agents for which NCI holds the IND, including cancer health disparities research, since these are readily available to translate to clinical evaluation in the NCI Experimental Therapeutics Clinical Trials Network (ETCTN).

PDXNet sites interact with the NCI Patient Derived Models Repository (PDMR) at the Frederick National Laboratory for Cancer Research (FNLCR) to expand the creation, characterization, and distribution of PDX models to the research community.

Examples of PDXNet collaborative projects, which required data harmonization and sharing by the PDTCs, and coordination by the PDCCC, include: 

• Treatment of the same PDX models with a single agent to evaluate the reproducibility of drug response in PDX models across all PDTC centers
• Multiple methods to determine potential genomic evolution over serial passages to evaluate PDX tumor stability in the context of multiple centers. Both projects required. 

Contact

Dr. Lori Henderson (hendersonlori@mail.nih.gov)