title: HER2 aberrations in cancer: implications for therapy.
abstract: Although anti-HER2 (human epidermal growth factor receptor 2) therapy is currently approved for breast, gastric, and gastroesophageal cancers overexpressing the HER2 protein or amplified for the HER2 gene, HER2 aberrations (gene amplification, gene mutations, and protein overexpression) are reported in other diverse malignancies. Indeed, about 1-37% of tumors of the following types harbor HER2 aberrations: bladder, cervix, colon, endometrium, germ cell, glioblastoma, head and neck, liver, lung, ovarian, pancreas, and salivary duct. Four HER2-targeted therapies have been approved for HER2-positive breast cancer: two antibodies (trastuzumab and pertuzumab), an antibody-drug conjugate (ado-trastuzumab emtansine), and a small molecule kinase inhibitor (lapatinib). In addition, afatinib, a small molecule kinase inhibitor that causes irreversible inhibition of EGFR (epidermal growth factor receptor) and HER2, was recently approved for EGFR-mutated non-small cell lung cancer. A large number of novel HER2-targeted agents are also in clinical trials. Herein we discuss the state of the art in understanding and targeting HER2 across anatomic tumor types.
authors.affiliation: Division of Hematology and Oncology, University of California, Moores Cancer Center, United States. Electronic address: M5yan@ucsd.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.affiliation: Division of Hematology and Oncology, University of California, Moores Cancer Center, United States.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Parker
authors.affiliation: Division of Hematology and Oncology, University of California, Moores Cancer Center, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Schwab
authors.affiliation: Division of Hematology and Oncology, University of California, Moores Cancer Center, United States.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000077716:Afatinib; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008453:Maytansine / Q000031:analogs & derivatives / Q000494:pharmacology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D000068878:Trastuzumab; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D000077716:Afatinib; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D008453:Maytansine; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: Ado-trastuzumab emtansine; Afatinib; Cancer; Human epidermal growth factor 2; Lapatinib; Pertuzumab; Target therapy; Trastuzumab