Figure 52. EGFR mutation status determines the outcome of erlotinib as a therapy.

(A) EGFR is a transmembrane receptor that has a tyrosine kinase (TK) domain. In the absence of EGF the normal receptor is in an inactive state. (B) When EGF binds, the TK domain undergoes a conformational change and becomes activated, generating signals for cell proliferation. (C) Cancer associated mutations in EGFR lead to hyperactivation of EGFR that represents a key driver of tumorigenesis. (D) The TK inhibitor erlotinib binds to EGFR and prevents downstream signalling. Therefore in cases where EGFR mutations are driving tumorigenesis, erlotinib can block this process. (E) The acquisition of a second mutation that prevents erlotinib binding leads to resistance to this inhibitor.