SOS2 and non-small cell lung carcinoma: Since these inhibitors target the SOS1-KRAS interaction, their effects include different mutation variants (G12C, G12V, G12S, G12A, and G12D), which have translated, preclinically, into decreased cellular proliferation across a wide range of KRAS-mutant tumors, notably NSCLC, PDAC, and CRC cell lines.253 In SOS2-knockout mouse models, BI-3406 was more effective at decreasing RAS-GTP levels and arresting cellular proliferation, suggesting that SOS2 activity is a potential resistance mechanism of KRAS inhibition.