EGFR and colorectal carcinoma: Abnormal EGFR gene copy number, protein expression of EGFR ligands, HER2 and MET gene amplifications, and activation of EGFR downstream cascade signaling pathways [including the mutations of RAS/BRAF/PIK3CA, the loss of PTEN, STAT3 phosphorylation, and epithelial-mesenchymal transition (EMT)], have been demonstrated to be associated with the primary resistance to anti-EGFR therapy in CRC (5, 7, 8).