Figure 3.

Proposed mechanism for acquired resistance to EGFR inhibitors by MET. (A): In erlotinib-sensitive cells, HER-3 phosphorylation by EGFR and downstream activation of PI3K/AKT is inhibited. (B): MET amplification phosphorylates HER-3 and activates PI3K/AKT in erlotinib-resistant cells. (C): MET inhibition by tivantinib and EGFR by erlotinib prevents phosphorylation of HER-3 and downstream activation of PI3K/AKT.

Abbreviations: EGFR, epidermal growth factor receptor; HER human epidermal growth factor receptor; PI3K, phosphoinositide 3-kinase.

Adapted from Nat Med 2007;13:675–677, with permission from Macmillan Publishers Ltd. Copyright 2007.