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Clinical Qualification of DNA Repair Defects as Biomarkers in Metastatic Prostate Cancer Using Integrated Genomics and Tissue Based Functional Assays

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Technical Report,30 Sep 2018,29 Sep 2019

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University of Washington Seattle United States

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Metastatic castration-resistant prostate cancer mCRPC is an incurable disease despite several agents being approved over the last decade. Understanding the inter-patient genomic heterogeneity in this disease is critical to advance to personalized cancer care based on predictive biomarkers. We and others have identified enrichment of homologous recombination HR mediated DNA repair defects in mCRPC, accounting for 20-25 cases, with inheritable defects in almost half of these cases. Ongoing clinical trials are studying the role of PARP inhibitors in this subpopulation. Particularly, BRCA2 mutations are known to be an independent poor prognostic factor for relapse in localized disease. Here, we propose to elucidate the prognostic and predictive impact of these mutations with regards to outcome from standard-of-care treatments for mCRPC, and to develop and clinically qualify functional tests to stratify mCRPC patients based on DNA repair damage proficiency, to improve the care of men with advanced prostate cancer.

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  • Medicine and Medical Research

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