Importantly, the KRASG12C inhibitor AMG510 (65) — but not TNO155, RMC-4550, nor the validated SHP2 degrader D26 (66) — completely abrogated ERK1/2 activation in KRASG12C MIA PaCa-2 pancreatic cancer cells, indicating that the incomplete p-ERK1/2 inhibition by TNO155 and RMC-4550 in KRASG12C mutant cells was likely due not to inadequate drug efficacy but rather to a limited reliance on SHP2 (Supplemental Figure 3C). This evidence concerns the gene MAPK3 and familial pancreatic carcinoma.