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Enhancing PARP inhibitor efficacy in ovarian cancer: targeting the PI3K/AKT/mTOR pathway

Yixuan Wang1, Qing Xia2, Xinjia Wang1

  • 1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Journal of Ovarian Research
|December 11, 2025
PubMed

Insights

Combining PI3K/AKT/mTOR inhibitors with PARP inhibitors shows promise for treating ovarian cancer. This strategy may overcome resistance and improve outcomes, especially in BRCA wild-type tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Ovarian cancer is a lethal malignancy often diagnosed late and resistant to therapies.
  • Poly (ADP-ribose) polymerase (PARP) inhibitors benefit tumors with homologous recombination deficiencies (e.g., BRCA mutations).
  • Clinical efficacy of PARP inhibitors is limited in homologous recombination-proficient or BRCA wild-type ovarian cancers.

Purpose of the Study:

  • To review evidence for combining PI3K/AKT/mTOR pathway inhibitors with PARP inhibitors in ovarian cancer.
  • To explore strategies for overcoming resistance to PARP inhibitors.
  • To highlight the role of the PI3K/AKT/mTOR axis in modulating PARP inhibitor sensitivity.

Main Methods:

  • Comprehensive review of preclinical and clinical studies.
  • Examination of natural and synthetic inhibitors of the PI3K/AKT/mTOR pathway.
  • Analysis of nanotechnology-based delivery systems for combination therapy.
  • Evaluation of biomarker-driven clinical trial data.

Main Results:

  • The PI3K/AKT/mTOR pathway is frequently dysregulated in ovarian cancer and impacts PARP inhibitor sensitivity.
  • Co-targeting PI3K/AKT/mTOR with PARP inhibitors enhances antitumor effects in preclinical models.
  • Nanotechnology and molecular stratification show potential in overcoming resistance.
  • Combination strategies are being investigated in clinical trials.

Conclusions:

  • Integrating PI3K/AKT/mTOR inhibition with PARP blockade is a promising strategy for ovarian cancer.
  • This combination approach may broaden the therapeutic application of PARP inhibitors.
  • Improved clinical outcomes are anticipated by targeting this pathway in ovarian cancer treatment.

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