The story of EGFR: from signaling pathways to a potent anticancer target.

Abstract

EGFR is a member of the ERBB family. It plays a significant role in cellular processes such as growth, survival and differentiation via the activation of various signaling pathways. EGFR deregulation is implicated in various human malignancies, and therefore EGFR has emerged as an attractive anticancer target. EGFR inhibition using strategies such as tyrosine kinase inhibitors and monoclonal antibodies hinders cellular proliferation and promotes apoptosis in cancer cells in vitro and in vivo. EGFR inhibition by tyrosine kinase inhibitors has been shown to be a better treatment option than chemotherapy for advanced-stage EGFR-driven non-small-cell lung cancer, yet de novo and acquired resistance limits the clinical benefit of these therapeutic molecules. This review discusses the cellular signaling pathways activated by EGFR. Further, current therapeutic strategies to target aberrant EGFR signaling in cancer and mechanisms of resistance to them are highlighted.