Patient-Derived Models of Cancer Program
Image of a patient-derived model system.
The Patient-Derived Models of Cancer (PDMC) program, funded through PAR-16-344, is developing and characterizing patient-derived models to define the biological mechanisms that drive cancer phenotype and response to perturbations. The program is testing and comparing distinct patient-derived models developed from common patient samples with the objective of improving the understanding of the strengths and limitations of different patient-derived models as representatives of human tumors.
Additionally, the program is undertaking systematic studies of patient-derived model parameters related to intrinsic tumor factors and microenvironmental pressures to explore fundamental cancer biology research questions. The goal of the PDMC is to improve patient-derived models for cancer biology research that may inform the development of novel cancer therapies.
PDMC News
In a Cell Stem Cell study supported by the PDMC and the Cancer Tissue Engineering Collaborative (TEC), Ding et al. generated 3D colorectal cancer patient-derived micro-organospheres that enable rapid high throughput drug testing. This technology overcomes limitations of patient-derived xenograft (PDX) models, such as data for clinical treatment decisions can be obtained within 14 days of diagnosis with the material from biopsy, retaining the tumor microenvironment, and capturing patient responses to immunotherapy.
A summary of this research focusing on the development of a new cancer model can be found in a Medical Xpress article.
Co-Chairs of the PDMC Steering Committee
Dr. Katerina Politi (Yale University) – Her PDMC project aims to provide fundamental insights into the evolution of EGFR mutant lung cancer under treatment and the mechanistic relationship between drug resistance and the tumor microenvironment. Ultimately, this research may lead to new therapeutic strategies for metastatic cancers.
Dr. Bryan Welm (University of Utah) - He is determining whether patient-derived models can recapitulate the repertoire of breast cancer phenotypes. Through a co-clinical study, he is also investigating whether they can functionally replicate patient responses to therapies.
NCI-Supported Resources Related to Patient-Derived Models
- PDX Finder – A comprehensive global catalogue of patient-derived xenograft (PDX) models and their associated data across resources
- NCI Patient -Derived Models Repository (PDMR) - A national repository of patient-derived models, including (PDXs), patient-derived tumor cell cultures and cancer associated fibroblasts, as well as patient-derived organoids
- PDXNet Portal – A database of PDX models, sequencing data, and PDX Minimum Information metadata tools generated by the PDXNet [inline link to NET Moonshot page] (which is funded by the Cancer Moonshot) for public use.
Funded Projects
| Institution | Principal Investigator(s) | Project Title |
|---|---|---|
| Cold Spring Harbor Laboratory – Jackson Laboratory | David Tuveson, Paul Robson | CSHL-JAX Patient-Derived Models of Pancreatic Cancer as Systems for Investigating Tumor Heterogeneity |
| Duke University | Xiling Shen, Shiaowen D. Hsu | Epigenomic Reprogramming in Patient Derived Models of Colorectal Cancer |
| Lurie Children's Hospital of Chicago | Xiao-Nan Li | Matching Panels of in vivo and in vitro Model System of Pediatric Brain Tumors |
| Oregon Health & Science University | Rosalie C. Sears, Jonathan Brody, Lisa M. Coussens, Emek Demir | Comparative Analysis between Patient-derived Models of Pancreatic Ductal Adenocarcinomas and Matched Tumor Specimens |
| University of Alabama at Birmingham | Christopher D. Willey, Jake Y. Chen, Xiangqin Cui, G. Yancey Gillespie, Anita Hjelmeland, Raj K. Singh | Biological Comparisons Among Three Derivative Models of Glioma Patient Cancers Under Microenvironmental Stress |
| University of California, San Francisco | John Kurhanewicz, Donna M. Peehl | Metabolic Imaging Comparisons of Patient-Derived Models of Renal Cell Carcinoma |
| University of Texas MD Anderson Cancer Center | Nora Navone, Yu Chen, Phillip A. Futreal | Patient-Derived Models of Prostate Cancer for Personalized Medicine |
| University of Texas Southwestern Medical Center | Sean J. Morrison | The Metabolic Regulation of Melanoma Metastasis |
| University of Utah | Bryan E. Welm, Gabor T. Marth, Katherine E. Varley | Longitudinal Models of Breast Cancer for Studying Mechanisms of Therapy Response and Resistance |
| Yale University | Katerina A. Politi, Don X. Nguyen | Uncovering the Biology of Resistance to TKI in EGFR Mutant Lung Cancer |