In CRC which is quadruple wild-type for KRAS, NRAS, BRAF and PI3KCA genes, HER2 gene amplification and activating mutations at the phosphorylation sites of the catalytic domain have been shown to bypass EGFR blockade by activating a compensatory signalling mechanism for cell survival (Kavuri et al., 2015; Belli et al., 2019). The gene discussed is EGFR; the disease is colorectal carcinoma.