Role of the interleukin 6 receptor family in epithelial ovarian cancer and its clinical implications

Biochim Biophys Acta. 2014 Apr;1845(2):117-25. doi: 10.1016/j.bbcan.2013.12.003. Epub 2014 Jan 2.

Abstract

Ovarian cancer is the most lethal gynecological malignancy, with few effective treatment options in most cases. Therefore, understanding the biology of ovarian cancer remains an important area of research in order to improve clinical outcomes. Cytokine receptor signaling through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is an essential component of normal development and homeostasis. However, numerous studies have implicated perturbation of this pathway in a range of cancers. In particular, members of the IL-6R family acting via the downstream STAT3 transcription factor play an important role in a number of solid tumors - including ovarian cancer - by altering the expression of target genes that impact on key phenotypes. This has led to the development of specific inhibitors of this pathway which are being used in combination with standard chemotherapeutic agents. This review focuses on the role of IL-6R family members in the etiology of epithelial ovarian cancer, and the application of therapies specifically targeting IL-6R signaling in this disease setting.

Keywords: Cytokine signaling; Epithelial; IL-6R; JAK–STAT pathway; Ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Female
  • Humans
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • Janus Kinases / genetics
  • Janus Kinases / metabolism
  • Molecular Targeted Therapy
  • Neoplasms, Glandular and Epithelial / etiology
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / etiology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Receptors, Interleukin-6 / genetics*
  • STAT3 Transcription Factor / biosynthesis*
  • Signal Transduction / genetics

Substances

  • Interleukin-6
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Janus Kinases