A recent preclinical study demonstrated EMT-induced resistance to sotorasib via IGFR-dependent, KRAS G12C-independent activation of the PI3K-AKT pathway in KRAS-mutated NSCLC cells, and a combination treatment with sotorasib plus the SHP2 inhibitor SHP099 and the PI3K inhibitor GDC-0941 effectively impaired the growth of KRAS G12C-mutant tumors [92]. The gene discussed is PIK3CA; the disease is non-small cell lung carcinoma.