Targeting the Subtype of Metastatic Prostate Cancer Deficient in DNA Repair Capacity
Technical Report,15 Aug 2018,14 Aug 2019
University of Washington Seattle United States
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This proposal will address the challenge of effectively treating mPC by exploiting specific tumor vulnerabilities conferred by defects in HR DNA repair. The objectives are supported by compelling data derived from the PCFSU2C Precision Medicine project, other sequencing efforts that assessed the molecular landscape of mCRPC, and striking clinical observations. We will aggressively target the subtype of DNA Repair Deficient HRD mCRPC to test the hypothesis that aberrations in key genes that repair DNA strand breaks by homologous recombination HR are predictive of meaningful clinical responses to FDA-approved genotoxic therapeutics e.g carboplatin and to emerging therapeutics PARP and WEE1 inhibitors. We will also test the hypothesis that men with mPC represent a population highly enriched for germ-line aberrations in DNA repair genes irrespective of racial background. The proposal will also develop strategies to enhance initial responses and assess mechanisms of resistance to genotoxic agents.
- Medicine and Medical Research