The epidermal growth factor receptor: structure-function informing the design of anticancer therapeutics
Details
Publication Year 2018-08-08, Volume 371, Issue #1, Page 1-19
Journal Title
Experimental Cell Research
Publication Type
Journal Article
Abstract
Research on the epidermal growth factor (EGF) family and the family of receptors (EGFR) has progressed rapidly in recent times. New crystal structures of the ectodomains with different ligands, the activation of the kinase domain through oligomerisation and the use of fluorescence techniques have revealed profound conformational changes on ligand binding. The control of cell signaling from the EGFR-family is complex, with heterodimerisation, ligand affinity and signaling cross-talk influencing cellular outcomes. Analysis of tissue homeostasis indicates that the control of pro-ligand processing is likely to be as important as receptor activation events. Several members of the EGFR-family are overexpressed and/or mutated in cancer cells. The perturbation of EGFR-family signaling drives the malignant phenotype of many cancers and both inhibitors and antagonists of signaling from these receptors have already produced therapeutic benefits for patients. The design of affibodies, antibodies, small molecule inhibitors and even immunotherapeutic drugs targeting the EGFR-family has yielded promising new approaches to improving outcomes for cancer patients. In this review, we describe recent discoveries which have increased our understanding of the structure and dynamics of signaling from the EGFR-family, the roles of ligand processing and receptor cross-talk. We discuss the relevance of these studies to the development of strategies for designing more effective targeted treatments for cancer patients.
Publisher
Elsevier
WEHI Research Division(s)
Structural Biology
PubMed ID
30098332
NHMRC Grants
NHMRC/1092788
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-08-15 03:28:52
Last Modified: 2019-12-03 03:23:38
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