Journal
EXPERT REVIEW OF HEMATOLOGY
Volume 2, Issue 4, Pages 399-414Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1586/ehm.09.31
Keywords
AML; hematological; leukemia; malignancies; mTOR inhibitors; PIM kinase; targeted therapy
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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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