COMPUTATIONAL APPROACH FOR IDENTIFYING A COMBINATION OF TWO DRUGS

摘要

The present invention relates to a method for identifying a therapeutic drug combination against a cancer, wherein the cancer comprises at least two alterations in at least two different, but crosstalking signaling pathways, the method comprising the steps of: a) providing a kinetic model of a biological network for said cancer comprising the at least two different, but crosstalking signaling pathways, wherein the kinetic model is generated by choosing a network topology, wherein the nodes of said topology represent biological entities selected from the group comprising genes, transcripts, peptides, proteins, protein modification states, small molecules, complexes, metabolites and modifications thereof, and the edges of said topology represent interactions between said entities, assigning kinetic laws and kinetic constants to the interactions and assigning concentrations to the biological entities, such that the kinetic model reflects the genome, epi-genome, proteome and/or transcriptome of said cancer, b) selecting test combinations from a plurality of known drugs, each test combination comprising at least two drugs, c) simulating the effect of each test combination on the biological network, thereby d) identifying from said test combinations a drug combination that acts against said cancer.