Genome-wide CRISPR screens identify PARP inhibitor sensitivity and resistance in prostate cancer

Prostate cancer tumors harboring BRCA1/2 mutations are exceptionally sensitive to PARP inhibitors, while genomic alterations in other DNA damage response (DDR) genes are less responsive. To identify previously unknown genes whose loss has a profound impact on PARP inhibitor response, researchers from Dana-Farber Brigham Cancer Center led a multinational effort to perform genome-wide CRISPR-Cas9 knockout screens. The study goal was to inform the use of PARP inhibitors beyond BRCA1/2-deficient tumors and support reevaluation of current biomarkers for PARP inhibition in prostate cancer.