Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [scRNA-seq]

KRAS G12C inhibitors (G12Ci) alone and in various combinations are being tested in multiple tumors with over-activation of the RAS/ERK pathway. KRAS plays a critical role in normal cell signaling; hence, G12Cis could influence the signaling pathways. We found that several novel pathways including Hippo pathways are upregulated upon MRTX849 treatment. Our results argue for testing KRAS G12C and TEAD inhibitor combinations in NSCLC patients. Overall design: Expression profiling by high throughput sequencing. To compare gene expression of tumor cells, and associated signaling pathways changes upon KRAS G12Ci and KRAS G12C+SHP2i drug resistance in patients sample. KRASG12C inhibitor, AMG510 KRASG12C inhibitor, MRTX849 SHP2 inhibitor, TNO155