New synthetic lethal interactions with PARP inhibition

A pair of papers could further support the use of synthetic lethality to help treat cancer. A paper in Nature highlights genes with potential synthetic lethal interactions with PARP inhibition, while another in Nature Communications suggests a new method that adds patient data to in vitro screening hits to find which synthetic lethal combinations are clinically relevant.

In the Nature paper, a Mount Sinai Hospital team and colleagues used CRISPR knockout screens to test sensitivity to PARP inhibitor Lynparza olaparib in cervical cancer, BRCA1-mutated triple-negative breast cancer and retinal pigment epithelium cell lines, and identified 73 high-confidence genes that could mediate resistance to PARP inhibitors. Three genes coding for the ribonuclease H2 (RNASEH2) enzyme complex -- subunit A (RNASEH2A), subunit B (RNASEH2B) and subunit C (RNASEH2C) -- were hits in all three cell lines...