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 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.
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York, USA.
Sarah A
SA
Wacker
Benjamin R
BR
Houghtaling
Olivier
O
Elemento
Tarun M
TM
Kapoor
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001897:Boronic Acids / Q000737:chemistry / Q000494:pharmacology; D000069286:Bortezomib; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011621:Pteridines / Q000737:chemistry / Q000494:pharmacology; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D059467:Transcriptome / Q000235:genetics*; D000097869:Polo-Like Kinase 1
D000970:Antineoplastic Agents; D001897:Boronic Acids; D000069286:Bortezomib; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D011719:Pyrazines; D000097869:Polo-Like Kinase 1; C518477:BI 2536