Tubers and tumors: rapamycin therapy for benign and malignant tumors.
Rapamycin and its derivatives represent a unique set of pharmaceutical agents being employed across a broad range of therapeutic indications including organ transplantation, cardiovascular disease, the treatment of harmartomas, and cancer. In cancer this family of drugs is unique as it exploits tumor-associated changes in cell metabolism. mTOR complex 1 (mTORC1), a protein kinase complex, is the major target of rapamycin, and is a key element of evolutionarily conserved pathways that regulate cellular metabolism in response to environmental nutrients and intracellular energy status. Upstream mTOR regulatory proteins -- the TSC tumor suppressor, the Rheb proto-oncogene, the hVps34 phophatidylinositol kinase, and the Rag GTPases -- determine tumor growth, metabolism, and apoptosis susceptibility. Novel compounds that target mTOR and PI3K enzymes may further enhance the efficacy in inhibiting this pathway in a number of human pathologies, particularly cancer.
Plas
David R
DR
Department of Cancer and Cell Biology, Genome Research Institute, University of Cincinnati, Cincinnati, OH, USA.
Thomas
George
G
D000596:Amino Acids / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002986:Clinical Trials as Topic; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D020752:Neurocutaneous Syndromes / Q000188:drug therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011506:Proteins; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism
D000596:Amino Acids; D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D011506:Proteins; D000090063:Proto-Oncogene Mas; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; C000715470:MAS1 protein, human