Targeting HER (ERBB) signaling in head and neck cancer: An essential update

• Type of Material: Article
• Authors: Jun Zhang, Emory University; Nabil Saba, Emory University; Georgia Chen, Emory University; Dong Shin, Emory University
• Language: English
• Date: 2015-11-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.mam.2015.07.001
• Title of Journal or Parent Work: Molecular Aspects of Medicine
• Volume: 45
• Start Page: 74
• End Page: 86
• Grant/Funding Information: JZ is an awardee of the T32 training grant (1T32CA160040-01A1, PI: DMS)
• Keywords: Science & Technology; Bispecific antibody; Squamous cell carcinoma; Biochemistry & Molecular Biology; Medicine, Research & Experimental; EGFR inhibitors; HER; Research & Experimental Medicine; Life Sciences & Biomedicine; Nuclear translocation; Receptor tyrosine kinase (RTK); Targeted therapy; SCCHN; ERBB; Cetuximab resistance; Crystal structure; Acquired resistance; Epidermal growth factor; Mutational landscape; EGFR
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Molecular; Health Sciences, Oncology

Abstract

HNC (head and neck cancer) remains the 6th most common carcinoma worldwide. The suboptimal survival and toxicities observed with conventional approaches warrant exploration of novel therapeutic strategies such as targeted therapies. Although targeting EGFR (epidermal growth factor receptor) with cetuximab demonstrated clinical promise, HER (human epidermal growth factor receptor) or ERBB (erythroblastic leukemia viral oncogene homolog) targeted therapy in HNC has overall been suboptimal to date in clinical settings. Overcoming the resistance as well as identifying new strategies therefore remains a significant challenge. In this review, we will discuss the emerging roles of HER members besides EGFR. A comprehensive "three-dimensional" view of HER signaling pathway from the importance of EGFR nuclear translocation to our maturing concept of receptors' "spatial regulation", as well as the interdependence and interaction among different HER members will also be addressed to complete an essential update of HER signaling in HNC.