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标题：A streamlined search technology for identification of synergistic drug combinations
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作者：Andrea Weiss ; Robert H. Berndsen ; Xianting Ding 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep14508
出版社：Springer Nature
摘要：A major key to improvement of cancer therapy is the combination of drugs. Mixing drugs that already exist on the market may offer an attractive alternative. Here we report on a new model-based streamlined feedback system control (s-FSC) method, based on a design of experiment approach, for rapidly finding optimal drug mixtures with minimal experimental effort. We tested combinations in an in vitro assay for the viability of a renal cell adenocarcinoma (RCC) cell line, 786-O. An iterative cycle of in vitro testing and s-FSC analysis was repeated a few times until an optimal low dose combination was reached. Starting with ten drugs that target parallel pathways known to play a role in the development and progression of RCC, we identified the best overall drug combination, being a mixture of four drugs (axitinib, erlotinib, dasatinib and AZD4547) at low doses, inhibiting 90% of cell viability. The removal of AZD4547 from the optimized drug combination resulted in 80% of cell viability inhibition, while still maintaining the synergistic interaction. These optimized drug combinations were significantly more potent than monotherapies of all individual drugs (p