Currently, however, EGFR antibody‐based therapies, as well as small‐molecule inhibitors, have been shown to exert a limited response and to frequently evoke resistance in patients due to (a) secondary mutations within the EGFR itself (e.g., T790M in NSCLC, and mutations found in the extracellular domain of cetuximab‐resistant colorectal cancers, Fig. 1B), (b) alterations in other kinases (e.g., c‐MET, PIK3CA, BRAF, MAPK1), or (c) the emergence of feedback regulatory loops and mechanisms that overcome EGFR kinase inhibition (reviewed in Mancini and Yarden, 2016). The gene discussed is EGFR; the disease is colorectal cancer.