title: mTOR kinase inhibitors as a treatment strategy in hematological malignancies.
abstract: The mammalian target of rapamycin (mTOR) kinase is a key element of intracellular signal transduction, responsible for the regulation of cell growth and proliferation. Since abnormal activation of the mTOR pathway was found in several tumors, including human malignancies, it may be an attractive target for antineoplastic treatment. The first identified mTOR inhibitor was rapamycin (sirolimus). Subsequently, the most potent rapamycin analogues (rapalogues), such as everolimus, temsirolimus and deforolimus, have been developed. After encouraging preclinical experiments, several clinical trials testing the rapalogues in monotherapy or in combinations with other cytotoxic agents have been conducted in patients with hematological malignancies. Results of these studies, described in this review, indicate that inhibition of the mTOR pathway may be a very promising strategy of anti-tumor treatment in several types of lymphomas and leukemias. Recently, a second generation of more effective mTOR inhibitors has been developed. These are currently being assessed in preclinical, Phase I or I/II clinical studies.
authors.affiliation: Department of Experimental Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Grzybowska-Izydorczyk
authors.forename: Piotr
authors.initials: P
authors.lastname: Smolewski
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus