Targeting HER2 in ovarian and uterine cancers: challenges and future directions

Gynecol Oncol. 2014 Nov;135(2):364-70. doi: 10.1016/j.ygyno.2014.09.003. Epub 2014 Sep 16.

Abstract

Targeting the human epidermal growth factor receptor 2 (HER2) has yielded major advances in breast cancer treatment. Accordingly, it has generated interest in targeting HER2 to treat gynecologic malignancies. Multiple studies have evaluated the rates of HER2 overexpression and/or amplification in ovarian and uterine cancers. HER2 has also been studied as a prognostic factor but resulting data has been contradictory. Moreover, clinical trials of HER2-directed therapies, including trastuzumab, pertuzumab, and lapatinib in ovarian and uterine cancers have been largely disappointing. Current research on HER2 in gynecologic malignancies has focused on identifying mechanisms of resistance and looking further into how HER2 signaling in gynecologic cancers differs from breast cancer. In this review, we highlight the existing data of targeting HER2 in ovarian and uterine carcinomas, many dating back more than a decade, and discuss future directions in pursuing HER2 as a potential target in these diseases.

Keywords: Endometrial cancer; HER2; Ovarian cancer; Targeted therapy; Trastuzumab; Uterine cancer.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma, Mucinous / drug therapy*
  • Adenocarcinoma, Mucinous / genetics
  • Ado-Trastuzumab Emtansine
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / genetics
  • Female
  • Genes, erbB-2 / genetics*
  • Humans
  • Lapatinib
  • Maytansine / analogs & derivatives
  • Maytansine / therapeutic use
  • Molecular Targeted Therapy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Quinazolines / therapeutic use
  • Trastuzumab
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / genetics

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Quinazolines
  • Lapatinib
  • Maytansine
  • pertuzumab
  • Trastuzumab
  • Ado-Trastuzumab Emtansine