This resistance may stem from (a) secondary mutations in the EGFR gene itself like the T790M mutation in non-small cell lung cancer or alterations in the extracellular domain associated with cetuximab resistance in colorectal cancer, (b) modifications in parallel signaling molecules including c-MET, PIK3CA, BRAF, and MAPK1, or (c) the activation of alternative signaling routes and compensatory feedback mechanisms that circumvent EGFR blockade.34 An emerging area of interest in cancer therapy is exploring how membrane trafficking affects the effectiveness of EGFR-targeted treatments. Here, EGFR is linked to colorectal cancer.