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Expert Rev Hematol. 2009 Aug;2(4):399-414. doi: 10.1586/ehm.09.31.

Potential of mTOR inhibitors as therapeutic agents in hematological malignancies.

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Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, 7979 Wurzbach Road, San Antonio, TX 78229, USA.


Despite significant advances in the treatment of hematological malignancies over the last decade, morbidity and mortality from these disorders remain high. New discoveries in the pathogenesis of these malignancies have led to better understanding of these diseases and new thinking in drug development. mTOR is a downstream effector of the PI3K/Akt (protein kinase B) signaling pathway that mediates cell survival and proliferation and is known to be deregulated in many cancers. Preclinical activity of mTOR inhibitors has been very promising in various hematological malignancies. Rapamycin analogs with relatively favorable pharmaceutical properties, including temsirolimus (CCI-779), everolimus (RAD001) and deforolimus (AP23573), are under clinical evaluations in patients with hematologic malignancies. They have shown encouraging results thus far and a favorable toxicity profile. Their utility, mainly as cytostatic agents, needs to be further explored in combination with pre-existing chemotherapeutic agents for various hematological malignancies.

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