title: Targeting HER family in HER2-positive metastatic breast cancer: potential biomarkers and novel targeted therapies.
abstract: HER2-targeted therapies have radically changed the prognosis of HER2-positive breast cancer over the last few years. However, resistance to these therapies has been a constant, leading to treatment-failure and new tumor progression. Recently, the kinase-impaired HER3 emerged as a pivotal player in oncogenic signaling, with an important role in both non-treated progression and treatment response. HER2/HER3 dimerization is required for full signaling potential and constitutes the key oncogenic unit. Also, when inhibiting PI3K/AKT pathway (as with anti-HER2 drugs) feedback mechanisms lead to a rebound in HER3 activity, which is one of the main roads to resistance. As current strategies to treat HER2-positive breast cancer are unable to inhibit this feedback response, two great promises emerged: the combination of targeted-therapies and drugs targeting HER3. In this article HER2 and HER3-targeted drugs and possible combinations between them, as well as the biomarkers to predict and monitor these drugs effect, are reviewed.
authors.affiliation: Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Inês de Paula Costa
authors.initials: Ide P
authors.lastname: Monteiro
authors.forename: Pedro
authors.initials: P
authors.lastname: Madureira
authors.forename: Alessandro
authors.initials: A
authors.lastname: de Vasconscelos
authors.forename: Daniel Humberto
authors.initials: DH
authors.lastname: Pozza
authors.forename: Ramon Andrade
authors.initials: RA
authors.lastname: de Mello
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000556:secondary / Q000628:therapy*; D019008:Drug Resistance, Neoplasm; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors / Q000235:genetics; D015398:Signal Transduction; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human
keywords: antineoplastic drug resistance; biomarkers; breast cancer; erbB-2 receptor; erbB-3 receptor; molecular targeted therapies; monoclonal antibodies; protein kinase inhibitors