title: HER3 as a Therapeutic Target in Cancer.
abstract: Targeting members of the human epidermal growth factor receptor family, especially EGFR and HER2, has been an established strategy for the treatment of tumors with abnormally activated receptors due to overexpression, mutation, ligand-dependent receptor dimerization and ligand-independent activation. Less attention has been paid to the oncogenic activity of HER3, although there is growing evidence that it mediates resistance to EGFR and HER2 pathway directed therapies. The main caveat for the development of effective HER3 targeted therapies is the absence of a strong enzymatic activity to target, as well as the limited potential for single-agent activity. In this review, we highlight the role of HER3 in cancer and, more specifically, in lung cancer. The basis for HER3 involvement in HER2 resistance and EGFR inhibition is discussed, as well as current pharmacologic strategies to combat HER3 inhibition.
authors.affiliation: Medical Oncology Department, Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, C/Viladomat 288, 08029, Barcelona, Spain. nkarachaliou@oncorosell.com.
authors.forename: Niki
authors.identifier: http://orcid.org/0000-0002-2378-0498
authors.initials: N
authors.lastname: Karachaliou
authors.affiliation: Departmemt of Oncology, Division of Experimental Medicine, IRCCS San Raffaele Hospital, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lazzari
authors.affiliation: Ospedale Santa Maria delle Croci, Ravenna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Verlicchi
authors.affiliation: Medical Oncology Department, Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, C/Viladomat 288, 08029, Barcelona, Spain.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Sosa
authors.affiliation: Germans Trias i Pujol Research Institute, Badalona, Spain.|Catalan Institute of Oncology, Germans Trias i Pujol University Hospital, Badalona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3