Fig. 1: LKB1 loss confers sensitivity to combined MAPK + MCL-1 inhibition in KRAS-mutant NSCLC models.
From: LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers
A Schema for testing sotorasib drug combinations. B Relative increased efficacy of sotorasib + AMG 176 combination compared to sotorasib alone (ΔAUC—see Fig. S2A for explanation) against KRASG12C-mutant NSCLC cell lines. Each dot represents an independent biological replicate, N = 4). Comparison of ΔAUC between KRAS-mutant NSCLC cell lines stratified according to LKB1 status. *p = 0.029 (C), *p = 0.032 (D), unpaired-nonparametric t test, 2-sided. KRAS-mutant NSCLC cell lines were treated with 0.1 µM of trametinib or 1 µM of sotorasib in combination with 1 µM of AMG 176 for up to 72 h and apoptosis was assessed by annexin positivity by flow cytometry (E, data are mean and S.E.M. of N = 3 biological replicates) or live-cell imaging (F, data are mean and S.E.M. of 3 technical replicates). For annexin positivity, percentage of apoptotic cells in vehicle group was used as a control and normalized to 0. Source data are provided as a Source Data file.
