HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies

Mol Diagn Ther. 2013 Apr;17(2):85-99. doi: 10.1007/s40291-013-0024-9.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Trastuzumab
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Receptor, ErbB-2
  • Trastuzumab