High-Throughput Screen of Advanced Prostate Cancer Organoids and PDX Preclinical Trials to Identify Single and Combination Therapies Correlated with Genotype
Abstract
Objective: Our goal is to guide the design of future clinical trials for aggressive prostate cancer and the optimum patient selection for those trials. Our objectives are 1) to establish pre-clinically validated efficacious drugs and drug combinations together with predictive molecular correlates when possible, and 2) analyze and provide to the prostate cancer research community a large data set encompassing CRPC drug responsiveness for genotypically and phenotypically characterized patient-derived samples. Impact: This innovative proposal is designed to address a major limitation in our knowledge concerning the breadth of therapeutic vulnerabilities for advanced prostate cancer and the molecular properties associated with drug responsiveness. If successful, we expect that novel combinations comprised of clinically translatable agents could proceed directly to biomarker-driven phase II clinical trials, addressing the PCRP Overarching Challenge to develop effective treatments and address mechanisms of resistance for men with high-risk or metastatic prostate cancer, and the PCRP Focus Area of Therapy and Mechanisms of Resistance and Response. Indeed, the NIH Clinical Center is well-poised to conduct such a trial. In addition, the availability of an extensive drug response database will provide to the community a platform that can be further leveraged for preclinical studies, bioinformatics/statistical mining, and mechanistic analysis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1194702
Entities
People
- Kathleen Kelly
Organizations
- Geneva Foundation