EGFR and colorectal carcinoma: Although EREG and AREG are predominant EGFR ligands expressed in CRC, and only a small fraction of high-affinity ligands is expressed [29], upon downstream activation of the EGFR/RAS/MAPK axis owing to a mutated KRAS effector, the expression of AREG and EREG ligands would be biologically irrelevant in terms of any benefit from cetuximab [8,20,21,45].