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Article Abstract

Determining mechanisms of drug action in human cells remains a major challenge. Here we describe an approach in which multiple-drug-resistant clones are isolated and transcriptome sequencing is used to find mutations in each clone. Further analysis of mutations common to more than one clone can identify a drug's physiological target and indirect resistance mechanisms, as indicated by our proof-of-concept studies of the cytotoxic anticancer drugs BI 2536 and bortezomib.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281560PMC
http://dx.doi.org/10.1038/nchembio.779DOI Listing

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