The objective response that was observed with sotorasib therapy in PDAC patients (21%)32 in the CodeBreak 100 trial was greater than that among patients with CRC (9.7%),376 but lower than the one observed for NSCLC (37.1%).369,370 Examination of data from CRC patients treated with KRAS G12C inhibitors indicates that, upon RAS inhibition, increased tyrosine kinase signaling within these tumors, coupled with the reactivation of receptors (particularly EGFR), diminishes the response to KRAS G12C inhibitors. Here, EGFR is linked to colorectal carcinoma.