Growth rate inhibition metrics correct for confounders in measuring sensitivity to cancer drugs.

ABSTRACT: Drug sensitivity and resistance are conventionally quantified by IC50 or Emax values, but these metrics are highly sensitive to the number of divisions taking place over the course of a response assay. The dependency of IC50 and Emax on division rate creates artefactual correlations between genotype and drug sensitivity, while obscuring valuable biological insights and interfering with biomarker discovery. We derive alternative small molecule drug-response metrics that are insensitive to division number. These are based on estimation of the magnitude of drug-induced growth rate inhibition (GR) using endpoint or time-course assays. We show that GR50 and GRmax are superior to conventional metrics for assessing the effects of small molecule drugs in dividing cells. Moreover, adopting GR metri

SUBMITTER: Hafner M 

PROVIDER: S-EPMC4887336 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature