000214138 001__ 214138
000214138 005__ 20181203024059.0
000214138 0247_ $$2doi$$a10.1038/srep14508
000214138 022__ $$a2045-2322
000214138 02470 $$2ISI$$a000361878600001
000214138 037__ $$aARTICLE
000214138 245__ $$aA streamlined search technology for identification of synergistic drug combinations
000214138 269__ $$a2015
000214138 260__ $$bNature Publishing Group$$c2015$$aLondon
000214138 300__ $$a11
000214138 336__ $$aJournal Articles
000214138 520__ $$aA 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 < 0.001, CI < 0.3).
000214138 700__ $$0245759$$g191745$$uSwiss Fed Inst Technol EPFL, Inst Chem Sci & Engn, Lausanne, Switzerland$$aWeiss, Andrea
000214138 700__ $$uSwiss Fed Inst Technol EPFL, Inst Chem Sci & Engn, Lausanne, Switzerland$$aBerndsen, Robert H.
000214138 700__ $$uShanghai Jiao Tong Univ, Sch Biomed Engn, Med X Res Inst, Shanghai 200030, Peoples R China$$aDing, Xianting
000214138 700__ $$aHo, Chih-Ming
000214138 700__ $$uSwiss Fed Inst Technol EPFL, Inst Chem Sci & Engn, Lausanne, Switzerland$$aDyson, Paul J.
000214138 700__ $$0240886$$g106613$$aVan Den Bergh, Hubert
000214138 700__ $$uVrije Univ Amsterdam, Med Ctr, Angiogenesis Lab, Dept Med Oncol, Amsterdam, Netherlands$$aGriffioen, Arjan W.
000214138 700__ $$aNowak-Sliwinska, Patrycja$$uSwiss Fed Inst Technol EPFL, Inst Chem Sci & Engn, Lausanne, Switzerland$$g168504$$0245027
000214138 773__ $$j5$$tScientific Reports$$q14508
000214138 909C0 $$0252359$$pGR-VDB
000214138 909CO $$particle$$ooai:infoscience.tind.io:214138$$pSB$$pSTI
000214138 917Z8 $$x135992
000214138 937__ $$aEPFL-ARTICLE-214138
000214138 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000214138 980__ $$aARTICLE