Author/Authors :
Wei، نويسنده , , Guo and Twomey، نويسنده , , David and Lamb، نويسنده , , Justin and Schlis، نويسنده , , Krysta and Agarwal، نويسنده , , Jyoti and Stam، نويسنده , , Ronald W. and Opferman، نويسنده , , Joseph T. and Sallan، نويسنده , , Stephen E. and den Boer، نويسنده , , Monique L. and Pieters، نويسنده , , Rob and Golub، نويسنده , , Todd R. and Armstrong، نويسنده , , Scott A.، نويسنده ,
Abstract :
Summary
esistance 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.
