Tubers and tumors: rapamycin therapy for benign and malignant tumors.

George Thomas, David R Plas

Journal: Current opinion in cell biology 2009;21(2):230-6

PMID: 19237273

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Department of Cancer and Cell Biology, Genome Research Institute, University of Cincinnati, Cincinnati, OH, USA.

DOI: 10.1016/j.ceb.2008.12.013

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MeSH Terms: Amino Acids, Antibiotics, Antineoplastic, Cardiovascular Diseases, Clinical Trials as Topic, Humans, Immunosuppressive Agents, Mechanistic Target of Rapamycin Complex 1, Multiprotein Complexes, Neoplasms, Neurocutaneous Syndromes, Phosphatidylinositol 3-Kinases, Proteins, Proto-Oncogene Mas, Signal Transduction, Sirolimus, TOR Serine-Threonine Kinases, Transcription Factors