Biological considerations and clinical applications of new HER2-targeted agents.
Over the past two decades, since the discovery of the human EGF receptor 2 (HER2) oncogene, the oncoprotein has become one of the best known and intensively studied tumor targets in oncology. In fact, laboratory findings were the basis for clinical proof-of-principle studies, whose results not only confirmed the relationship between gene amplification and an aggressive tumor phenotype but also demonstrated that the poor prognosis associated with receptor overexpression could be improved. Indeed, the success in treating patients with HER2-positive breast cancer extends to those with early as well as advanced disease. Nonetheless, not all tumors respond to treatment targeting the receptor; disease progression also occurs after initially responding to anti-HER2 therapy. This article focuses on the biology of HER2 and three novel agents currently in clinical trials that target HER2 beyond disease progression.
Higa
Gerald M
GM
Schools of Pharmacy and Medicine, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9162, USA.
Singh
Vikramjit
V
Abraham
Jame
J
D000080044:Ado-Trastuzumab Emtansine; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002986:Clinical Trials as Topic; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D008453:Maytansine / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000068878:Trastuzumab
D000080044:Ado-Trastuzumab Emtansine; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab