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

• Authors: Jun Zhang, Emory University; Nabil Saba, Emory University; Georgia Chen, Emory University; Dong Shin, Emory University
• Journal Title: Molecular Aspects of Medicine
• Volume: Volume 45
• Publisher: Elsevier | 2015-11-01, Pages 74-86
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.mam.2015.07.001
• Subjects: Biology, Molecular; Health Sciences, Oncology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Medicine, Research & Experimental; Research & Experimental Medicine; EGFR; HER; ERBB; SCCHN; Targeted therapy; Squamous cell carcinoma; Epidermal growth factor; Receptor tyrosine kinase (RTK); Acquired resistance; EGFR inhibitors; Nuclear translocation; Mutational landscape; Cetuximab resistance; Bispecific antibody; Crystal structure

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.