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Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer

Andrea Weiss; Xianting Ding; Judy R. van Beijnum; Ieong Wong; Tse J. Wong; Robert H. Berndsen; Olivier Dormond; Marchien Dallinga; Li Shen; Reinier O. Schlingemann; Roberto Pili; Chih-Ming Ho; Paul J. Dyson; Hubert van den Bergh; Arjan W. Griffioen; Patrycja Nowak-Sliwinska
Angiogenesis · Vol. 18, Issue 3 · pp. 233-244 · 2015

Abstract

Drug combinations can improve angiostatic cancer treatment efficacy and enable the reduction of side effects and drug resistance. Combining drugs is non-trivial due to the high number of possibilities. We applied a feedback system control (FSC) technique with a population-based stochastic search algorithm to navigate through the large parametric space of nine angiostatic drugs at four concentrations to identify optimal low-dose drug combinations. This implied an iterative approach of in vitro testing of endothelial cell viability and algorithm-based analysis. The optimal synergistic drug combination, containing erlotinib, BEZ-235 and RAPTA-C, was reached in a small number of iterations. Final drug combinations showed enhanced endothelial cell specificity and synergistically inhibited proliferation ( p p p p

Bibliographic Information

JournalAngiogenesis
PublisherSpringer
Publication Date2015-07-01
Publication Year2015
Volume18
Issue3
Pages233-244
Document TypeJournal Article
eISSN1573-7209
DOI10.1007/s10456-015-9462-9

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NARA Access Coverage1997-01-01~Current
Journal Homepagehttps://www.springer.com/journal/10456
Publisher PageOpen Publisher Page
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