A Third Shot at EGFR: New Opportunities in Cancer Therapy.

Epidermal growth factor receptor (EGFR) inhibitors were among the first type of targeted agents discovered in cancer and currently constitute the standard of care for a wide range of lung and colon malignancies. However, the therapeutic progress achieved with these drugs has been accompanied by the identification of an ever-increasing number of acquired resistance mechanisms that inevitably appear in nearly all patients. Increased knowledge on EGFR biochemistry, cellular crosstalk, and resistance pathways provides an opportunity to establish effective combination therapies and discover novel-acting inhibitors that prevent or overcome therapeutic resistance. One such strategy is the selective blockade of circulating growth factors such as EGF. In this review, we address the uses and limitations of approved EGFR inhibitors and explore the potential of drug combinations and new third avenues to block the activation of the EGFR.