@article{88724741d8084d0d8a7946788b9d382e,
title = "Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance",
abstract = "Drug resistance remains a major obstacle to successful cancer treatment. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in acute lymphoblastic leukemia (ALL) cells. The screen indicated that the mTOR inhibitor rapamycin profile matched the signature of GC sensitivity. We tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells and found that it sensitized to GC-induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis and that the combination of rapamycin and glucocorticoids has potential utility in lymphoid malignancies. Furthermore, this approach represents a strategy for identification of promising combination therapies for cancer.",
keywords = "Animals, Cell Line, Tumor, Cell Survival/drug effects, Databases, Genetic, Dexamethasone/pharmacology, Dose-Response Relationship, Drug, Drug Combinations, Drug Resistance, Neoplasm, Gene Expression/drug effects, Genomics, Glucocorticoids/pharmacology, Green Fluorescent Proteins/metabolism, Humans, Mice, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins/metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy, Proto-Oncogene Proteins c-bcl-2/metabolism, Sirolimus/metabolism",
author = "Guo Wei and David Twomey and Justin Lamb and Krysta Schlis and Jyoti Agarwal and Stam, {Ronald W} and Opferman, {Joseph T} and Sallan, {Stephen E} and {den Boer}, {Monique L} and Rob Pieters and Golub, {Todd R} and Armstrong, {Scott A}",
note = "Funding Information: We thank Mari Nishino, Jinyan Du, and Paula Bernasconi for assistance. We thank Eric Smith and Elise Porter for help with artwork, editing, and administrative assistance. We also thank the German COALL (coordinated by G. Janka-Schaub, Children's Hospital Eppendorf, Hamburg, Germany) study groups for providing samples. This work was supported by The Leukemia Lymphoma Society (S.A.A.), the Damon Runyon Cancer Research Foundation (S.A.A. and G.W.), and the National Cancer Institute (NCI grants K08 CA92551 and PO1 CA068484). ",
year = "2006",
month = oct,
doi = "10.1016/j.ccr.2006.09.006",
language = "English",
volume = "10",
pages = "331--42",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}