KRAS inhibitor-resistance in MET-amplified KRASG12C 1 non-small cell lung cancer induced by RAS- and non-RAS-mediated cell signaling mechanism

Treatment with KRASG12C inhibitors such as sotorasib can produce substantial regression of tumors in some patients with non-small cell lung cancer (NSCLC). These patients require alternative treatment after acquiring resistance to the inhibitor. The mechanisms underlying this acquired resistance are unclear. The purpose of this study was to identify the mechanisms underlying acquired sotorasib resistance, and to explore potential treatments for rescuing patients with sotorasib-resistant KRASG12C NSCLC cells. H23ARC11 cell lines as resistant clones of sotorasib-sensitive KRAS G12C NSCLC H23 cells were obtained by exposing to increasing concentrations of sotorasib for nine months. Gene expression analysis was performed on ClariomS Human (Affymetrix) Chips.