High-Throughput Screen of Advanced Prostate Cancer Organoids and PDX Preclinical Trials to Identify Single and Combination Therapies Correlated with Genotype
Abstract
Despite the advances in our knowledge of prostate cancer (PC) biology and the widespread use of new FDA approved drugs (e.g. abirateroneacetate (AA), enzalutamide (ENZA), cabazitaxel, Radium 223, and Sipuleucel T ), approximately 27,000 men will still die this year of advanced PC1. Essentially no patients with metastatic PC are cured of their disease. Thou, substantial research efforts continue to be directed toward identifying new targets and therapeutics for metastatic castration resistant PC (mCRPC), it is challenging to develop new effective therapies for mCRPC: 1) There are multiple agents for the same target but no agents for other key factors. 2) Majority of new trials evaluate single agents and not combinations despite clear evidence in other malignancies of superior efficacy of combinations. 3) There are limited numbers of patients with mCRPC enrolling in clinical studies, a fact that impedes the breadth of drugs tested and the pace of evaluation. 4)There is a growing body of evidence demonstrating that mCRPC exhibits substantial inter-individual heterogeneity with respect to underlying molecular drivers. Only a few trials are designed using precision medicine paradigms that select patients based on molecular predictors of response and consequently the future optimal deployment of a therapeutic is hindered. We will perform high throughput screen using PC organoids to identify active combinatorial therapies and validate the outcome in vivo in patient derived xenografts clinical trial.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1125514
Entities
People
- Eva Corey
Organizations
- University of Washington