A common resistance mechanism to anti-EGFR therapies identified by a number of research groups in preclinical cancer models of the colon, the breast, the prostate and the brain involves activation of the PI3K/AKT signalling pathway either as a consequence of the loss of phosphatase and tensin homologue or of increased insulin-like growth factor type 1 receptor activity [12,15-19]. The gene discussed is EGFR; the disease is cancer.