Besides the KRAS-BRAF-PIK3CA mutational status, EGFR epiregulin (EREG) and ampiregulin (AREG) ligands' expression in primary CRC tumours has been shown to significantly predict clinical outcome in KRAS WT mCRC patients treated with cetuximab, indicating ligand-driven autocrine oncogenic EGFR signaling [27], [28]. This evidence concerns the gene EGFR and colorectal carcinoma.