Hypothesis and Theory ARTICLE
Rethink of EGFR in Cancer with Its Kinase Independent Function on Board
- 1Department of Biology and Biochemistry, College of Natural Science and Mathematics, University of Houston, United States
The epidermal growth factor receptor (EGFR) is one of most potent oncogenes that are commonly altered in cancers. As a receptor tyrosine kinase, EGFR’s kinase activity has been serving as the primary target for developing cancer therapeutics, namely the EGFR inhibitors including small molecules targeting its ATP binding pocket and monoclonal antibodies targeting its ligand binding domains. EGFR inhibitors have produced impressive therapeutic benefits to responsive types of cancers. However, acquired and innate resistances have precluded current anti-EGFR agents from offering sustainable benefits to initially responsive cancers and benefits to EGFR-positive cancers that are innately resistant. Recent years have witnessed a realization that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. This new knowledge has offered a different angle of understanding of EGFR in cancer and opened a new avenue of targeting EGFR for cancer therapy. There are already many excellent reviews on the role of EGFR with a focus on its kinase-dependent functions and mechanisms of resistance to EGFR targeted therapies. The present opinion aims to initiate a fresh discussion about the function of EGFR in cancer cells by laying out some unanswered questions pertaining to EGFR in cancer cells, by rethinking the unmet therapeutic challenges from a view of EGFR’s KID function, and by proposing novel approaches to target the KID functions of EGFR for cancer treatment.
Keywords: EGFR, kinase independent function, mitophagy, Cell Survival, Cancer
Received: 29 Apr 2019;
Accepted: 06 Aug 2019.
Copyright: © 2019 Weihua and Thomas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mx. Zhang Weihua, University of Houston, Department of Biology and Biochemistry, College of Natural Science and Mathematics, Houston, United States, firstname.lastname@example.org