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Updated: Jul 24, 2025

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Guiding model-driven combination dose selection using multi-objective synergy optimization
Jana L Gevertz1, Irina Kareva2
1Department of Mathematics and Statistics, The College of New Jersey, Ewing, New Jersey, USA.
Abstract:
Despite the growing appreciation that the future of cancer treatment lies in combination therapies, finding the right drugs to combine and the optimal way to combine them remains a nontrivial task. Herein, we introduce the Multi-Objective Optimization of Combination Synergy - Dose Selection (MOOCS-DS) method for using drug synergy as a tool for guiding dose selection for a combination of preselected compounds. This method decouples synergy of potency (SoP) and synergy of efficacy (SoE) and identifies Pareto optimal solutions in a multi-objective synergy space. Using a toy combination therapy model, we explore properties of the MOOCS-DS algorithm, including how optimal dose selection can be influenced by the metric used to define SoP and SoE. We also demonstrate the potential of our approach to guide dose and schedule selection using a model fit to preclinical data of the combination of the PD-1 checkpoint inhibitor pembrolizumab and the anti-angiogenic drug bevacizumab on two lung cancer cell lines. The identification of optimally synergistic combination doses has the potential to inform preclinical experimental design and improve the success rates of combination therapies. Jel classificationDose Finding in Oncology.
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