title: HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies.
abstract: HER2 or ErbB2 is a member of the epidermal growth factor family and is overexpressed in subsets of breast, ovarian, gastric, colorectal, pancreatic, and endometrial cancers. HER2 regulates signaling through several pathways (Ras/Raf/mitogen-activated protein kinase and phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin pathways) associated with cell survival and proliferation. HER2-overexpressed and/or gene-amplified tumors are generally regarded as biologically aggressive neoplasms. In breast, cervical, endometrial, and ovarian cancer, there have been several studies linking the amplification of the c-erbB2 gene with chemoresistance and overall poor survival. Tyrosine kinase inhibitors and immunotherapy with monoclonal antibodies targeting HER2 hold promise for patients harboring these aggressive neoplasms. Trastuzumab combined with cytotoxic chemotherapy agents or conjugated with radioactive isotopes is currently being investigated in clinical trials of several tumor types.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, LSOG 305, P.O. Box 208063, New Haven, CT 06520-8063, USA.
authors.forename: Diana P
authors.initials: DP
authors.lastname: English
authors.forename: Dana M
authors.initials: DM
authors.lastname: Roque
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000068878:Trastuzumab; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab