GCRC Frontiers in Cancer Research Lecture Series

Patient‐derived models of breast cancer and functional oncology

Bryan E. Welm, PhD
Associate Professor
Department of Surgery
Investigator
Huntsman Cancer Institute
University of Utah

The goal of the Welm Lab is to develop and utilize patient-derived models, including xenografts (PDX) and organoids (PDO), for functional precision oncology and preclinical cancer research. The hypothesis is that patient-derived models maintain salient molecular and genomic features of tumors, and when studied co-clinically, will enable patients to be better matched with effective therapies. The Welm lab has established a bank of PDO models that are used in moderate throughput screens of FDA-approved and NCI Investigational New Drugs. Effective “lead” therapies observed in the organoid assay are then validated in vivo using PDX models predicted to be responders or non-responder. For each lead therapy, genomic data are utilized to identify proteomic, gene expression and/or mutational signatures associated with drug response. In addition, a clinical study is being performed to evaluate the feasibility of functional precision oncology for breast cancer patients. PDX and PDO models are generated from newly diagnosed TNBC patients, and their models are tested against a library of 50 cancer drugs. The models and patient tumors are also analyzed for genomic variants and gene expression profiles, which are used to identify targeted therapies that may be effective against the patient’s tumor. The goal is to evaluate the feasibility of determining drug sensitivity profiles of patient-derived models within a clinically-relevant timeframe, and to determine the actionability of these data within a clinical setting.