title: HER3, serious partner in crime: therapeutic approaches and potential biomarkers for effect of HER3-targeting.
abstract: The human epidermal growth factor receptor (HER) family members are targeted by a growing numbers of small molecules and monoclonal antibodies. Resistance against the epidermal growth factor receptor (EGFR) and HER2-targeting agents is a clinically relevant problem forcing research on optimizing targeting of the HER family. In view of its overexpression in tumors, and compensatory role in HER signaling, HER3 has gained much interest as a potential additional target within the HER family. It is the only member of the HER family lacking intrinsic tyrosine kinase activity and therefore its role in cancer has long been underestimated. Drugs that block HER3 or interfere with HER3 dimer signaling, including fully human anti-HER3 antibodies, bispecific antibodies and tyrosine kinase inhibitors (TKIs), are currently becoming available. Several compounds have already entered clinical trial. In the meantime potential biomarkers are tested such as tumor analysis of HER3 expression, functional assays for downstream effector molecules and molecular imaging techniques. This review describes the biology and relevance of HER3 in cancer, agents targeting HER3 and potential biomarkers for effect of HER3-targeting.
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Arjan
authors: A
authors: Kol
authors: Department of Hospital and Clinical Pharmacy, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Anton G T
authors: AG
authors: Terwisscha van Scheltinga
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Hetty
authors: H
authors: Timmer-Bosscha
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Laetitia E
authors: LE
authors: Lamberts
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Frederike
authors: F
authors: Bensch
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Elisabeth G E
authors: EG
authors: de Vries
authors: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: c.p.schroder@umcg.nl.
authors: Carolina P
authors: CP
authors: Schröder
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011799:Quinazolines / Q000627:therapeutic use; D020893:Receptor, ErbB-3 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C548875:AZD 8931; D018033:Antibodies, Bispecific; D015415:Biomarkers; D011799:Quinazolines; C573311:MM-111; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3
keywords: Biomarkers; HER3; Molecular imaging; Monoclonal antibodies; Resistance; Tyrosine kinase inhibitors