title: Potential of mTOR inhibitors as therapeutic agents in hematological malignancies.
abstract: 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.
authors.affiliation: 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. sankhala@uthscsa.edu
authors.forename: Kamalesh
authors.initials: K
authors.lastname: Sankhala
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases