Genome-Scale CRISPR Screens Reveal DNA Repair Dependencies That Sensitize Hepatocellular Carcinoma to Oxaliplatin
Hanyue Ouyang·Ming Shi·Dongsheng Wen·Lichang Huang·Z Z Wu·ZhiCheng Lai·Minke He·Wenchao Wu·Diyun Huang
Background: Most patients with hepatocellular carcinoma (HCC) present with advanced disease and have limited systemic treatment options. Oxaliplatin shows clinical activity in HCC but its effectiveness is frequently curtailed by intrinsic and acquired resistance. We sought to systematically identify genetic vulnerabilities that increase oxaliplatin sensitivity in HCC. Methods: Genome-scale negative-selection CRISPR–Cas9 screens were conducted in two genetically distinct HCC cell lines (Hep3B and