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The rationale for mTOR inhibition in epithelial ovarian cancer

Xuan Bich Trinh1, Peter A van Dam, Luc Y Dirix

  • 1St Augustinus Hospital, Translational Cancer Research Group-Antwerp, Wilrijk-Antwerp, Belgium.

Expert Opinion on Investigational Drugs
|November 6, 2009
PubMed

Insights

The AKT/mTOR pathway is overexpressed in ovarian cancer, making mTOR inhibitors promising for treatment. Preclinical studies show these inhibitors have anti-tumor and anti-angiogenic effects, supporting ongoing clinical trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The AKT/mTOR signaling pathway is frequently overexpressed in human epithelial ovarian cancer.
  • This pathway represents an attractive therapeutic target for ovarian cancer treatment.

Purpose of the Study:

  • To review the rationale and preclinical findings for using mTOR inhibitors in ovarian cancer.
  • To explore the potential of mTOR inhibitors in combination therapies and the adjuvant setting.

Main Methods:

  • Review of preclinical data from in vitro and in vivo mouse models of ovarian cancer.
  • Analysis of findings from ongoing Phase I-II clinical trials of mTOR inhibitors in ovarian cancer patients.

Main Results:

  • In vitro studies confirmed the role of the AKT/mTOR pathway in ovarian cancer.
  • In vivo administration of mTOR inhibitors in ovarian cancer xenografts demonstrated significant antitumoral and antiangiogenic effects.
  • Ongoing clinical trials are evaluating mTOR inhibitors, often in combination with cytotoxic agents.

Conclusions:

  • mTOR inhibitors show significant preclinical promise for ovarian cancer therapy.
  • Combinations of mTOR inhibitors with other targeted therapies warrant investigation.
  • mTOR inhibitors may have potential in the adjuvant setting due to the lack of standard maintenance therapy in ovarian cancer.
  • Identification of predictive biomarkers is crucial for the successful clinical development of mTOR inhibitors.

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