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Using transcriptome sequencing to identify mechanisms of drug action and resistance.


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.

SUBMITTER: Wacker SA 

PROVIDER: S-EPMC3281560 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Using transcriptome sequencing to identify mechanisms of drug action and resistance.

Wacker Sarah A SA   Houghtaling Benjamin R BR   Elemento Olivier O   Kapoor Tarun M TM  

Nature chemical biology 20120212 3


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. ...[more]

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