Potential drug repurposing of ruxolitinib to inhibit the JAK/STAT pathway for the treatment of patients with epithelial ovarian cancer

J Obstet Gynaecol Res. 2023 Nov;49(11):2563-2574. doi: 10.1111/jog.15761. Epub 2023 Aug 10.

Abstract

Aim: This review aimed to describe the potential for therapeutic targeting of the JAK/STAT signaling pathway by repurposing the clinically-approved JAK inhibitor ruxolitinib in the patients with epithelial ovarian cancer (OC) setting.

Methods: We reviewed publications that focus on the inhibition of the JAK/STAT pathway in hematological and solid malignancies including OC.

Results: Preclinical studies showed that ruxolitinib effectively reduces OC cell viability and metastasis and enhances the anti-tumor activity of chemotherapy drugs. There are a number of recent clinical trials exploring the role of JAK/STAT inhibition in solid cancers including OC. Early results have not adequately supported efficacy in solid tumors. However, there are preclinical data and clinical studies supporting the use of ruxolitinib in combination with both chemotherapy and other targeted drugs in OC setting.

Conclusion: Inflammatory conditions and persistent activation of the JAK/STAT pathway are associated with tumourigenesis and chemoresistance, and therapeutic blockade of this pathway shows promising results. For women with OC, clinical investigation exploring the role of ruxolitinib in combination with chemotherapy agents or other targeted therapeutics is warranted.

Keywords: JAK/STAT; ascitic fluid; chemoresistance; ovarian cancer; ruxolitinib.

Publication types

  • Review

MeSH terms

  • Carcinoma, Ovarian Epithelial / drug therapy
  • Drug Repositioning
  • Female
  • Humans
  • Janus Kinases* / metabolism
  • Janus Kinases* / pharmacology
  • Ovarian Neoplasms* / drug therapy
  • STAT Transcription Factors / metabolism
  • STAT Transcription Factors / pharmacology
  • Signal Transduction

Substances

  • Janus Kinases
  • ruxolitinib
  • STAT Transcription Factors

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