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Invited Commentary
November 5, 2020

A CHIP in the Armor of Cell-Free DNA–Based Predictive Biomarkers for Prostate Cancer

Author Affiliations
  • 1Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor
JAMA Oncol. 2021;7(1):111-112. doi:10.1001/jamaoncol.2020.5140

A greater understanding of tumor biology, coupled with clinical genomics, has revolutionized the treatment of patients with advanced cancers, including prostate cancer. A key example is the discovery that sequence variants or other loss of function alterations in homologous recombination DNA (HRD) repair genes are present in approximately 23% of men with metastatic castration-resistant prostate cancer (CRPC). Loss of HRD genes leads to reliance of tumor cells on single-strand DNA repair. One class of proteins responsible for single-strand DNA repair is the poly(ADP) ribose polymerase (PARP) proteins. Importantly, HRD gene mutations plus PARP inhibition leads to cell death, an example of synthetic lethality.

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