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Review
mTOR, A New Therapeutic Target in Acute Myeloid Leukemia
Récher Christian, Dos Santos Cédric, Demur Cécile and Payrastre Bernard.
volume 4 | issue 11
November 2005Pages: 1540 - 1549
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The mTOR (mammalian target of rapamycin) serine threonine kinase is involved in the regulation of the cell cycle, apoptosis and angiogenesis. mTOR inhibitors (rapamycin, or analogues such as CCI-779, RAD001, AP23573), which have been shown to have a potent anti-neoplastic effect in many solid tumour models, are now being used in clinical trials. Recent data have shown that the mTOR pathway is also aberrantly activated in hematological malignancies including acute myeloid leukemia (AML). This disease still has a bad prognosis and new therapeutic strategies are required. Rapamycin, used at low concentrations, induces the profound inhibition of AML cell clonogenic properties in 60% of cases while sparing their normal counterparts. Moreover, clinical responses have been achieved in poor-risk AML patients. In this review, we discuss the possible mechanisms of mTOR activation, the mechanisms involved in the inhibition of cell proliferation by rapamycin, the possible resistance mechanisms and ways of improving rapamycin efficacy in the context of AML.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.