Drug–gene Interaction Screens Coupled to Tumor Data Analyses Identify the Most Clinically Relevant Cancer Vulnerabilities Driving Sensitivity to PARP Inhibition

Abstract

This study identifies tumor genetic backgrounds where to expand the use of PARPis beyond mutations in <i>BRCA1</i> or <i>BRCA2</i>. This is achieved by combining the output of unbiased genome-wide loss-of-function CRISPR-Cas9 genetic screens with bioinformatics analysis of biallelic losses of the identified genes in public tumor datasets, unveiling loss of the DNA repair gene <i>XRCC3</i> as a potential biomarker of PARPi sensitivity in prostate cancer.