The Seven Stones

The connectivity map of drug combinations

How does the connectivity of biochemical networks influence the response to drug combinations?

To address this question, 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 (Lehár et al, 2007) . 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 dependancy can be used to learn how biological systems are connected as well as to elucidate the mechanism of multi-drug treatments, which are increasingly preferred for many diseases.

It will be interesting to see how far this kind of analysis takes us in the real world: how much will ‘off-target’ effects confound the analysis? To what extent is the mapping between network topologies and response surfaces a one-to-one function? Further, it would be important to extend this idea to three or more drug components. (Yeh and Kishony, 2007)


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