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The response to drug combinations critically depends on how their biological targets are connected, according to a study published online in Molecular Systems Biology. Understanding how multi-drug combinations work is vital in medicine, in order to rationalize their use and discover novel targets.
Joseph Lehár and colleagues analyzed the response of yeast and human tumour cell lines to thousands of drug pairs, and compared these experimental data to a computational model. By systematically measuring the biological effects of drug pairs over a range of concentrations, 'response surfaces' could be constructed. This strategy enabled the authors to establish a clear relationship between the shape of the biological 'response surface' and the type of connection linking the targeted biochemical pathways. This study provides a general framework to analyze the effects of drug combinations and will help future researchers to better understand and develop effective multi-drug therapeutics. Author contact: Joseph Lehár (CombinatoRx Incorporated, Cambridge, MA, USA)
E-mail: jlehar@combinatorx.com Editorial contact: Thomas Lemberger (Molecular Systems Biology, Germany)
E-mail: msb@embo.org
Abstract available online. (C) Molecular Systems Biology press release.
Message posted by: Trevor M. D'Souza
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