Patient-Derived Xenograft (PDX) Models to Advance Novel Cancer Therapies
Researchers at Northwestern University and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University now have new and robust models for testing novel cancer therapies thanks to a joint effort by the Center for Developmental Therapeutics (CDT), the Feinberg School of Medicine Department of Obstetrics and Gynecology, and the Lurie Cancer Center’s Pathology Core Facility (PCF).
The Patient-Derived Xenograft (PDX) tumor repository allows many basic oncology research questions to be addressed using models that more closely resemble human cancer. The PDX tumor models are established from the transplantation of fresh human tumor specimen from a cancer patient directly into a mouse. The tumors are only passaged in mice and never see plastic, thereby eliminating a major cause of selection bias and creating a model that is much closer to human cancer than traditional xenograft models.
Currently, novel therapies often fail in clinical trials despite the significant effort and resources aimed at drug discovery and preclinical testing. The standard model in testing these drugs has been transplantation of human cancer cell lines preserved in vitro. PDX tumors, unlike xenograft tumors established from cancer cell lines, preserve key features of a specific cancer such as invasiveness, desmoplastic reaction, tumor vasculature and cellular diversity. The PDX tumors that grow are propagated in mice by transplanting tumor fragments or in some cases (e.g. glioma) tumor suspensions created using a tumor dissociator. These models can in some cases be grown under the skin (subcutaneously), or under the kidney capsule (subrenally), and in some cases the tumors may be grown orthotopically by engrafting or inoculating back into the same organ from where the tumor originated.
The current repository already has multiple PDX tumor models of 10 different types of cancer: glioblastoma, breast, renal, bladder, pancreatic, colon, ovarian, endometrial, mesothelioma and leukemia. This was made possible through tumors samples obtained from over 40 cancer patients by the diligence of various Lurie Cancer Center clinicians and the Pathology Core Facility. It is anticipated that this repository will continue to expand to include additional types of cancer as well as more models within each tumor type.
The close connection and specialized skill set between CDT and PCF enabled the team to overcome challenges inherent in developing a PDX tumor repository, such as providing a broad availability of cancer models and increased success rate of implantation.
The PDX repository will provide immediate opportunities for the Northwestern research community to test novel anticancer compounds and probe novel mechanisms and biomarkers, but it will soon be available to the broader cancer research community. Molecular profiling of each model is planned and Northwestern researchers are encouraged to begin using the confirmed models in their own research.
For more information, please visit the Center for Developmental Therapeutics website: www.cdt.northwestern.edu/pdx
*Patients participating in the PDX program were fully consented with NU IRB approved forms utilized by PCF. During the consent process, they were asked to authorize the collection of data that would be used for scientific research in a manner consistent with 45 CFR 46, the applicable federal regulation for the protection of human research subjects.