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Epigenetic Compound Library Screen Identifies Ibrutinib as an Inhibitor of Ovarian Clear Cell Carcinoma Viability

Yue Ma1, Kristie-Ann Dickson1, Farhana A Sarker1

  • 1Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.

Cancer Medicine
|April 9, 2026
PubMed
Abstract

Insights

Ovarian clear cell carcinoma (OCCC) shows sensitivity to ibrutinib, a Bruton's Tyrosine Kinase (BTK) inhibitor. This finding suggests potential new treatments for this rare ovarian cancer subtype.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Ovarian clear cell carcinoma (OCCC) is linked to endometriosis and characterized by specific genetic mutations.
  • OCCC often exhibits resistance to conventional chemotherapy and has limited treatment options.
  • While immunotherapy shows promise, further therapeutic strategies are needed for OCCC.

Purpose of the Study:

  • To identify novel drug treatments for ovarian clear cell carcinoma (OCCC).
  • To screen epigenetic compounds for their efficacy against OCCC cell lines.
  • To validate potential drug candidates in advanced cell models and investigate their mechanisms of action.

Main Methods:

  • Screened OCCC and non-OCCC cell lines using an epigenetic drug library at two concentrations.
  • Selected drugs that preferentially inhibited OCCC cell viability.
  • Validated findings in 2D and 3D bioprinted models and explored associated signaling pathways.

Main Results:

  • OCCC cell lines demonstrated higher sensitivity to the Bruton's Tyrosine Kinase (BTK) inhibitor ibrutinib compared to non-OCCC cells.
  • Ibrutinib's efficacy varied among different OCCC cell lines in both 2D and 3D cultures.
  • Ibrutinib impacted PI3K/AKT/mTOR cell survival signaling in a subset of OCCC cell lines, indicating potential activity through other pathways.

Conclusions:

  • Ibrutinib, currently used for B cell disorders, shows potential for treating solid tumors like OCCC.
  • These findings align with clinical observations of ibrutinib's effectiveness in low-grade serous ovarian cancer.
  • Ibrutinib warrants further investigation as a therapeutic agent for specific rare ovarian cancer subtypes.
Keywords:
Bruton's tyrosine kinasedrug repurposingibrutinibovarian clear cell carcinoma

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