title: New developments in mammalian target of rapamycin inhibitors for the treatment of sarcoma.
abstract: Although sarcomas account for a small portion of solid malignancies, currently, there are few treatment options for sarcomas, particularly for advanced disease. The mammalian target of rapamycin (mTOR), a serine-threonine protein kinase in the phosphatidylinositol 3-kinase/serine/threonine protein kinase Akt signaling pathway, has an important role in the regulation of protein synthesis, cell proliferation, angiogenesis, and metabolism. Alterations of the mTOR signaling pathway are common in malignancies, including several types of sarcoma. Therefore, mTOR is a potentially important therapeutic target in these diseases. Rapamycin and its analogs (rapalogs) are effective anticancer agents in a broad range of preclinical models. Clinical trials with these agents alone and in combination with other anticancer agents, including chemotherapy and targeted therapies, have demonstrated potential clinical benefit in several types of sarcoma. The evidence from both preclinical and clinical studies supports further study of mTOR-targeting rapalogs in the treatment of various subtypes of sarcoma.
authors.affiliation: Division of Medical Hematology/Oncology, Northwestern University, Chicago, Illinois, USA. m-agulnik@northwestern.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Agulnik
mesh_terms: D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012509:Sarcoma / Q000188:drug therapy*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases