The Scientific Library recently hosted its first virtual discussion of 2021, featuring Yvonne A. Evrard, Ph.D., operations manager for the NCI Patient-Derived Models Repository (PDMR) at NCI at Frederick and the Frederick National Laboratory for Cancer Research (FNL). These virtual discussions are one way the Library uses its position as a research information hub to engage scientific researchers through collaboration, interaction, and discussion.
The PDMR is a national repository of cancer models sourced from patients. It is being developed by the NCI to serve as a resource for academic and commercial investigators in their drug discovery and development research efforts.
Evrard began by explaining the group’s origins. In 2012, NCI invited researchers from academia and commercial spaces to discuss their preclinical needs. From this, NCI determined that there was a need for early passage, clinically annotated preclinical cancer models. When the PDMR first began, the group focused on solid tumor histologies. It received the first tumor in 2013, and the first 100 patient-derived xenografts (PDXs), a type of laboratory model, were made available to the research community four years later, in 2017. Evrard emphasized that all of the models were made within the Biological Testing Branch at NCI at Frederick and that multiple groups across NCI at Frederick and FNL are involved in characterizing them.
The repository aims to derive 1,000 PDX models, a milestone it is well on its way toward attaining, Evrard said. The repository has been working to increase the number of models from common cancer diagnoses but has also focused efforts on gathering rare histologies and generating models from patients of diverse racial and ethnic backgrounds so it can capture a representative slice of the clinical population. Evrard said the repository also aims to identify and add new data to make it more useful to researchers. The team also hopes to develop human leukocyte antigen typing and develop PDX models from blood-based malignancies like leukemias, lymphomas, and myelomas.
In the meantime, Evrard said the team generates other models, like patient-derived cell lines and patient-derived organoids. They can also provide DNA and RNA to researchers. The PDMR has a database of available models at pdmr.cancer.gov, plus there is an accompanying link to a user guide to assist those who may be new to searching the interface. Users can search for cancer in a specific body system, or they can search for models with a specific mutation, like one in KRAS, or models from patients who were treatment naïve or previously treated. The website has an email to the PDMR if users have any additional questions.
Evrard then explained the complex process of how models are cataloged and stored in the repository, an extensive sequence that involves receiving samples from clinical centers across the country, culturing the cells to generate the models, verifying the models’ integrity through pathology and genetic sequencing, and recording and scrutinizing the data through rigorous quality control processes.
Evrard added that most of the models are made on-site, but others come from external parties that deposit them in the PDMR because it is prohibitively expensive for them to create and store in-house models long-term. The PDMR will accept models via email requests, but there is a set of criteria that must be met beforehand.
The virtual discussion concluded with Evrard revisiting some future goals of the repository, such as its work on methods development for blood-based malignancies within the Biological Testing Branch (NCI at Frederick) and how these will affect meeting the goal of 1,000 PDXs. Ideally, the PDMR would like to increase the number of models for which they have three model types—a PDX, an in vitro organoid, and a cell line. This scenario will allow researchers to grow the cell lines and organoids on-site, which is a faster and less expensive endeavor than PDX work in mice. They can use those cell lines to do drug or biomarker screening to narrow down which models best meet their criteria, then order the matched PDX from the same originating patient.
Before signing off, Evrard encouraged all NCI and FNL staff to contact the PDMR if they have any ideas on how to improve the usability of the patient-derived models to benefit the research community.
“I feel that this is an incredibly powerful resource to the scientific community, as researchers from a range of disciplines such as bioinformatics, basic research, and translational research can use the models and model data to advance cancer research,” she said.
If your team provides services to NCI at Frederick and FNL researchers and staff and is interested in participating in a virtual discussion or a discussion panel to share expertise about your services with the NCI at Frederick community, contact the Library.
Matt Stirling is a biosciences informationist in the Scientific Library, where he provides search & reference assistance to library patrons, teaches classes on information resources, and coordinates the Daily Science News service. The Scientific Library assists in all phases of the research process by providing information services, resources, and training to all NCI at Frederick and FNL employees.