The CRISPR screens in KRASG12D preclinical models have implicated EGFR and SHP2 as possible resistance mechanisms.87 FLAGSHP-1 is investigating the combination of the SHP2 inhibitor ERAS-601 and cetuximab in patients with advanced solid tumors.79,88 Preclinical studies of the SOS1 inhibitor BI-3406 have demonstrated MAPK inhibition in pancreatic cancer and CRC cells harboring a variety of KRAS mutations. This evidence concerns the gene SOS1 and familial pancreatic carcinoma.