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Virtual clinical trials identify effective combination therapies in ovarian cancer

Emilia Kozłowska1,2, Tuulia Vallius3, Johanna Hynninen4

  • 1Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Scientific Reports
|December 12, 2019
PubMed

Insights

Virtual clinical trial simulations identified novel ovarian cancer drug combinations. Resensitizing chemoresistant cells proved more effective than targeting apoptosis or platinum bioavailability, guiding future oncology research.

Area of Science:

  • Oncology
  • Computational Biology
  • Pharmacology

Background:

  • High failure rate in translating preclinical findings to clinical success in oncology.
  • Platinum-taxane chemotherapy is a standard treatment for ovarian cancer but faces resistance.
  • Need for effective combinatorial therapies to overcome platinum resistance in high-grade serous ovarian cancer.

Purpose of the Study:

  • To develop a mathematical framework for virtual clinical trial simulations.
  • To estimate the added value of combinatorial treatments in ovarian cancer.
  • To identify targeted therapies that can overcome platinum resistance when combined with platinum-taxane.

Main Methods:

  • Mathematical modeling and virtual clinical trial simulations approach.
  • Evaluation of three drugs targeting platinum resistance mechanisms.
  • Modeling drug effectiveness based on in vitro, in vivo, and early clinical trial data.

Main Results:

  • Drugs resensitizing chemoresistant cells demonstrated superior efficacy compared to those targeting apoptosis or platinum bioavailability.
  • The benefit of biomarker stratification in clinical trials is contingent on drug efficacy and tumor composition.
  • Identified specific drug combinations with potential to overcome platinum resistance.

Conclusions:

  • Virtual clinical trial simulations offer a valuable framework for testing drug combinations and optimizing clinical trial designs in solid cancers.
  • Resensitization strategies are promising for overcoming platinum resistance in ovarian cancer.
  • Biomarker-guided approaches are crucial but depend on drug and tumor characteristics.

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