BRAF and colorectal carcinoma: Those mutations cause permanent activation of the RAS (RAS/RAF/MAPK) pathway and predict resistance to anti-EGFR therapy.[15,16] As the direct downstream target of KRAS in the RAS pathway, BRAF mutated frequently in CRC.[17] Approximately 8% of CRC carry the BRAF V600E mutation, which determines resistance to the anti-EGFR therapy and is associated with poor prognosis in the MSS CRC.[18,19] DNA mismatch repair (MMR) system controls the newly synthesized DNA strands and corrects polymerase misincorporation events.