Alexandra O Sokolova1,2,3, Heather H Cheng4,5. 1. Department of Medicine, University of Washington, Washington, USA. 2. Clinical Research Division, Fred Hutchinson Cancer Research Center, 825 Eastlake Ave E, Seattle, WA, 98109, USA. 3. VA Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA, 98108, USA. 4. Department of Medicine, University of Washington, Washington, USA. hhcheng@uw.edu. 5. Clinical Research Division, Fred Hutchinson Cancer Research Center, 825 Eastlake Ave E, Seattle, WA, 98109, USA. hhcheng@uw.edu.
Abstract
PURPOSE OF REVIEW: This review summarizes recent advances in prostate cancer (PCa) genetics. RECENT FINDINGS: Upwards of 20% of metastatic castration-resistant prostate tumors (mCRPC) carry homologous recombination (HR) repair gene mutations, of which ~ 10% are germline (inherited). Another ~ 5% exhibit microsatellite instability (MSI-H) and/or mismatch repair deficiency (MMRd). Pembrolizumab is approved for tumors with MMRd, thus patients with mCRPC and MMRd are candidates for pembrolizumab. Emerging data indicate that platinum chemotherapy and poly ADP-ribose polymerase inhibitors (PARPi) are effective in PCa exhibiting HR deficiency. NCCN guidelines now recommend germline and somatic tumor testing in specific clinical scenarios due to treatment and family implications. Genetic testing in PCa patients may inform prognosis, treatment options, and have implications for family counseling. PARPi, platinum chemotherapy, and immune checkpoint inhibitors are promising targeted therapies for PCa with specific molecular features. Therapeutic advances, along with importance to relatives, are driving genetic testing in prostate cancer.
PURPOSE OF REVIEW: This review summarizes recent advances in prostate cancer (PCa) genetics. RECENT FINDINGS: Upwards of 20% of metastatic castration-resistant prostate tumors (mCRPC) carry homologous recombination (HR) repair gene mutations, of which ~ 10% are germline (inherited). Another ~ 5% exhibit microsatellite instability (MSI-H) and/or mismatch repair deficiency (MMRd). Pembrolizumab is approved for tumors with MMRd, thus patients with mCRPC and MMRd are candidates for pembrolizumab. Emerging data indicate that platinum chemotherapy and poly ADP-ribose polymerase inhibitors (PARPi) are effective in PCa exhibiting HR deficiency. NCCN guidelines now recommend germline and somatic tumor testing in specific clinical scenarios due to treatment and family implications. Genetic testing in PCapatients may inform prognosis, treatment options, and have implications for family counseling. PARPi, platinum chemotherapy, and immune checkpoint inhibitors are promising targeted therapies for PCa with specific molecular features. Therapeutic advances, along with importance to relatives, are driving genetic testing in prostate cancer.
Entities:
Keywords:
BRCA; Genetics; Germline testing; PARPi; Prostate cancer
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