A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Virtual clinical trials identify effective combination therapies in ovarian cancer
Tekijät: Kozlowska E, Vallius T, Hynninen J, Hietanen S, Farkkila A, Hautaniemi S
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2019
Journal: Scientific Reports
Tietokannassa oleva lehden nimi: SCIENTIFIC REPORTS
Lehden akronyymi: SCI REP-UK
Artikkelin numero: ARTN 18678
Vuosikerta: 9
Sivujen määrä: 9
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-019-55068-z
Rinnakkaistallenteen osoite: 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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
