title: Human epidermal growth factor receptor 3 in head and neck squamous cell carcinomas.
abstract: Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptor (HER) family. The main characteristic of HER3 is that it does not possess tyrosine kinase activity, unlike other HERs. The role of HER3 in tumorigenesis has now been recognized, particularly in head and neck squamous cell carcinomas (HNSCCs). Despite conflicting studies, HER3 was found to be overexpressed in HNSCC samples, and correlates with disease progression and poor survival, especially when it is coexpressed with other HERs. HER3 is a significant factor in HNSCC treatment resistance. Indeed, HER3 is a major mechanism described for cetuximab resistance because of modification of epidermal growth factor receptor (EGFR) internalization and by phosphotidylinositol-3-kinase (PI3K)/AKT signaling pathway activation. HER3 also affects resistance to tyrosine kinase inhibitors (TKIs) and thereby promotes treatment escape and radiotherapy resistance by activation of the survival signaling pathway. To counteract this, pharmacologic inhibitors of HER3 are currently in development and could significantly improve HNSCC treatment. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2412-E2418, 2016.
authors.affiliation: ENT and Head and Neck Surgery Department, Huriez Hospital, University of Lille, Lille, France.|Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, Inserm U908, IRCL, Lille, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Rysman
authors.affiliation: ENT and Head and Neck Surgery Department, Huriez Hospital, University of Lille, Lille, France.|Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, Inserm U908, IRCL, Lille, France.
authors.forename: François
authors.initials: F
authors.lastname: Mouawad
authors.affiliation: Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, Inserm U908, IRCL, Lille, France.
authors.forename: Abigaëlle
authors.initials: A
authors.lastname: Gros
authors.affiliation: Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, Inserm U908, IRCL, Lille, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Lansiaux
authors.affiliation: ENT and Head and Neck Surgery Department, Huriez Hospital, University of Lille, Lille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Chevalier
authors.affiliation: Tumorigenesis and Resistance to Treatment Unit, Centre Oscar Lambret, Inserm U908, IRCL, Lille, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Meignan
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D000068818:Cetuximab / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3; D051057:Proto-Oncogene Proteins c-akt; D000068818:Cetuximab
keywords: cetuximab; head and neck squamous cell carcinoma (HNSCC); human epidermal growth factor receptor 3 (HER3); radiotherapy; resistance; tyrosine kinase inhibitor