Fig. 7
From: RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms
Primary resistance to KRASG12C inhibitors. (A) The primary resistance mechanisms identified include KEAP1 co-mutations, ROS1 single-nucleotide variants, secondary RAS mutations, and a high PD-L1 tumor proportion score (TPS) [208]. (B) Co-alterations in KEAP1, SMARCA4, and CDKN2A have been associated with lower objective response rates, while co-alterations involving STK11 and DNA damage response (DDR) genes have been linked to better objective responses [13]. (C) Co-alterations in TP53, STK11, KEAP1, PIK3CG, POLE, BRCA2, SMAD4, CDKN2A, DNMT3A, MYC, BRCA1, BRINP3, and PTEN have been linked to either improved or reduced objective response rates [211]