title: Biomarkers for Predicting Response to Anti-HER2 Agents.
abstract: The HER2 receptor is amplified or overexpressed in approximately 20% of all breast cancers, but despite significant efforts of the clinical research community and a growing number of anti-HER2 agents, a significant number of patients with HER2-positive breast cancer either progress or suffer disease relapse within 5-10 years. The development of robust biomarkers that predict response to anti-HER2 agents is therefore an important clinical need to prevent overtreatment and to enable earlier assignment of patients to more optimal therapies. Here we review some of the recent advances in the field by focusing on pathways mediating resistance to anti-HER2 therapies, and the role of the immune system and cancer stem cells in therapy response. We also review preoperative treatment strategies and research paradigms that show promise in identifying novel biomarkers of response while also enabling the delineation of the mechanisms underlying clinical benefit from anti-HER2 therapies.
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Vinay
authors.initials: V
authors.lastname: Varadan
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Sandoval
authors.affiliation: Seidman Cancer Center, Cleveland, OH, USA. Lyndsay.Harris@UHhospitals.org.|School of Medicine, Case Western Reserve University, Cleveland, OH, USA. Lyndsay.Harris@UHhospitals.org.
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018579:Patient Selection; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Cancer stem cells; ErbB2; Genomics; HER2; Immune system; Preoperative therapy; Proteomics; Targeted therapy