A1 Refereed original research article in a scientific journal
Virtual clinical trials identify effective combination therapies in ovarian cancer
Authors: Kozlowska E, Vallius T, Hynninen J, Hietanen S, Farkkila A, Hautaniemi S
Publisher: NATURE PUBLISHING GROUP
Publication year: 2019
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: ARTN 18678
Volume: 9
Number of pages: 9
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-019-55068-z
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/43910527
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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