Using transcriptome sequencing to identify mechanisms of drug action and resistance

SA Wacker, BR Houghtaling, O Elemento… - Nature chemical …, 2012 - nature.com
SA Wacker, BR Houghtaling, O Elemento, TM Kapoor
Nature chemical biology, 2012nature.com
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.
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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