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Virtual Clinical Trials Identify Effective Combination Therapies in Ovarian Cancer by KozÅowska, Emilia; Vallius, Tuulia; Hynninen, Johanna; Hietanen, Sakari; Färkkilä, Anniina; Hautaniemi, Sampsa is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract A major issue in oncology is the high failure rate of translating preclinical results in successful clinical trials. Using a virtual clinical trial simulations approach, we present a mathematical framework to estimate the added value of combinatorial treatments in ovarian cancer. This approach was applied to identify effective targeted therapies that can be combined with the platinum-taxane regimen and overcome platinum resistance in high-grade serous ovarian cancer. We modeled and evaluated the effectiveness of three drugs that target the main platinum resistance mechanisms, which have shown promising efficacy in vitro, in vivo, and early clinical trials. Our results show that drugs resensitizing chemoresistant cells are superior to those aimed at triggering apoptosis or increasing the bioavailability of platinum. Our results further show that the benefit of using biomarker stratification in clinical trials is dependent on the efficacy of the drug and tumor composition. The mathematical framework presented herein is suitable for systematically testing various drug combinations and clinical trial designs in solid cancers.

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Author

KozÅowska, Emilia; Vallius, Tuulia; Hynninen, Johanna; Hietanen, Sakari; Färkkilä, Anniina; Hautaniemi, Sampsa

Publisher

Springer Science and Business Media LLC; London: Nature Publishing Group; [London]: Springer Nature; Nature Publishing Group; Society for Mining, Metallurgy and Exploration Inc.; Research Square; Springer Nature; Island Press (ISSN 2045-2322)

Published

2019

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)