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Using transcriptome sequencing to identify mechanisms of drug action and resistance

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 iden...

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Detalles Bibliográficos
Autores principales: Wacker, Sarah A., Houghtaling, Benjamin R., Elemento, Olivier, Kapoor, Tarun M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281560/
https://www.ncbi.nlm.nih.gov/pubmed/22327403
http://dx.doi.org/10.1038/nchembio.779
Descripción
Sumario: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 cytotoxic anti-cancer drugs, BI 2536 and bortezomib.