TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000361445
  • Gene Name:MTOR
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:mTOR signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB12387
  • Drug Name:OSI-027
  • Drug Method:down-regulated the gene expression the gene expression

Disease basic infommation

  • Disease:leukemia
  • Tissue:cell lines (K562, KT1, BV173 cells,Ba/F3)

Other information

  • Title:Induction of autophagy by dual mTORC1-mTORC2 inhibition in BCR-ABL-expressing leukemic cells
  • Journal:Autophagy
  • Published:2010
  • PubMed ID:20699667
  • Abstract:In recent years, there have been substantial research advances on the mechanisms by which BCR-ABL transforms hematopoietic cells and promotes leukemic cell growth and survival. Among the diverse signaling cascades activated by BCR-ABL, the mTOR pathway plays a critical role in mRNA translation of genes that promote leukemogenesis and mitogenic responses. We have recently shown that dual targeting of mTORC1 and mTORC2 complexes using a catalytic mTOR inhibitor, OSI-027, results in generation of potent antileukemic effects against BCR-ABL transformed cells. Such effects were also seen in cells expressing the T315I mutation, which is resistant to all currently approved BCR-ABL kinase inhibitors. Our studies also demonstrate that such dual catalytic inhibition of mTORC2 and mTORC1 complexes in BCR-ABL-expressing K562 cells results in induction of autophagy, and that inhibition of the autophagic process using chloroquine promotes apoptosis of these cells. Altogether, our studies suggest that autophagy may be a limiting factor for the induction of apoptosis during dual mTORC2-mTORC1 targeting, in at least some types of BCR-ABL-expressing cells and have raised the potential of combinations of catalytic inhibitors of mTOR with autophagy inhibitors for the treatment of refractory Ph(+) leukemias.
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