Mutations in EGFR or low expression of EGFR or AREG (amphiregulin)/EREG (epiregulin), key ligands in the EGFR-specific autocrine loop, cause loss of target for anti-EGFR therapy, representing one of the major ways by which EGFR resistance develops in NSCLC and CRC. This evidence concerns the gene AREG and non-small cell lung carcinoma.