GNAS and colorectal carcinoma: In summary, these findings suggest that, in BRAFV600E CRC, COX2–SRC–β-catenin signaling does not overlap with EGFR–BRAF–MAPK signaling and it is treatment with BRAF ± MEK or EGFR targeted therapies that triggers the compensatory upregulation of a pre-existing COX2–PGE2–GPCR–GNAS autocrine loop, which in turn activates SRC (Fig. 5k).