title: Utility of mTOR inhibition in hematologic malignancies.
abstract: The mammalian target of rapamycin (mTOR) is an intracellular serine/threonine kinase that exists as a downstream component of numerous signaling pathways. The activation of mTOR results in the production of proteins involved in cell metabolism, growth, proliferation, and angiogenesis. Aberrant activation of mTOR signaling has been identified in a number of cancers, and targeted inhibition of mTOR has been successful in achieving tumor responses, prolonging progression-free survival, and increasing overall survival in various oncologic patient populations. In particular, persistent activation of mTOR signaling has been identified in cell lines and patient samples with leukemias, Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), and Waldenström's macroglobulinemia (WM). In vitro and preclinical studies using agents that inhibit mTOR signaling have demonstrated cytostatic and cytotoxic effects in these hematologic malignancies, suggesting that mTOR is a rational target for therapy in these disease states. In addition, the combination of mTOR inhibitors with traditional therapies may help to overcome the development of resistance and may improve response rates over those seen with established regimens through synergistic or additive effects. Inhibitors of mTOR signaling currently are being investigated in clinical trials of hematologic malignancies as single agents and as components of combination regimens. Thus far, promising results have been seen with the application of mTOR inhibitors as single agents in patients with relapsed or refractory leukemia, HL, NHL, MM, and WM.
authors.affiliation: Department of Lymphoma/Myeloma, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. ayounes@mdanderson.org
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Nousheen
authors.initials: N
authors.lastname: Samad
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D015536:Down-Regulation; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015854:Up-Regulation; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy / Q000378:metabolism
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases