title: Targeting HER3 using mono- and bispecific antibodies or alternative scaffolds.
abstract: The human epidermal growth factor receptor 3 (HER3) has in recent years been recognized as a key node in the complex signaling network of many different cancers. It is implicated in de novo and acquired resistance against therapies targeting other growth factor receptors, e.g., EGFR, HER2, and it is a major activator of the PI3K/Akt signaling pathway. Consequently, HER3 has attracted substantial attention, and is today a key target for drugs in clinical development. Sophisticated protein engineering approaches have enabled the generation of a range of different affinity proteins targeting this receptor, including antibodies and alternative scaffolds that are either mono- or bispecific. Here, we describe HER3 and its role as a key tumor target, and give a comprehensive review of HER3-targeted proteins currently in development, including discussions on the opportunities and challenges of targeting this receptor.
authors.affiliation: a Division of Protein Technology, School of Biotechnology, KTH-Royal Institute of Technology, SE , Stockholm.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Malm
authors.affiliation: b Affibody AB, SE, Stockholm , Sweden.|c Department of Immunology , Genetics and Pathology, Uppsala University , Uppsala , Sweden.
authors.forename: Fredrik Y
authors.initials: FY
authors.lastname: Frejd
authors.affiliation: a Division of Protein Technology, School of Biotechnology, KTH-Royal Institute of Technology, SE , Stockholm.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ståhl
authors.affiliation: a Division of Protein Technology, School of Biotechnology, KTH-Royal Institute of Technology, SE , Stockholm.
authors.forename: John
authors.initials: J
authors.lastname: Löfblom
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D006801:Humans; D020893:Receptor, ErbB-3
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3
keywords: Affibody molecules; ErbB3; HER3; alternative scaffolds; bispecific antibodies; monoclonal antibodies; protein therapeutics; tumor targeting