Patent ID: 8560243

Claim:
A method of determining a therapeutic index of a drug in a biological sample comprising: applying a plurality of levels of said drug to said biological sample; measuring transcripts of a plurality of genes at different levels of said plurality of levels of said drug in said biological sample to obtain a first profile of graded drug response; applying said plurality of levels of said drug to a test sample, wherein said test sample is the same as said biological sample except that a target pathway is not functional; measuring transcripts of said plurality of genes in said test sample at different levels of said plurality of levels of said drug, to obtain a second profile of graded drug response; based at least on said first profile of graded drug response, determining C target , a minimum effective concentration of said drug needed to induce a target threshold response in a target pathway, wherein said target threshold response in the target pathway comprises at least a two-fold induction or repression of transcripts of genes in the plurality of genes in said target pathway; based at least on said second profile of graded drug response, determining C off-target , a minimum toxic concentration of said drug needed to induce an off-target threshold response in at least one off-target pathway, wherein said off target threshold response in the off-target pathway comprises at least a two-fold induction or repression of transcripts of genes in the plurality of genes in said off-target pathway; and determining said therapeutic index (TI) according to a formula: TI=C off-target /C target ; wherein the therapeutic index is relied upon as measurement of activity of the drug in the target pathway and the off-target pathway.