Plas David R, Thomas George
Department of Cancer and Cell Biology, Genome Research Institute, University of Cincinnati, Cincinnati, OH, USA.
Curr Opin Cell Biol. 2009 Apr;21(2):230-6. doi: 10.1016/j.ceb.2008.12.013. Epub 2009 Feb 23.
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.
雷帕霉素及其衍生物是一类独特的药剂，被广泛应用于多种治疗适应症，包括器官移植、心血管疾病、错构瘤治疗和癌症。在癌症治疗中，这类药物很独特，因为它利用了肿瘤相关的细胞代谢变化。mTOR复合物1（mTORC1）是一种蛋白激酶复合物，是雷帕霉素的主要靶点，也是进化保守通路的关键元件，该通路可根据环境营养物质和细胞内能量状态调节细胞代谢。上游mTOR调节蛋白——TSC肿瘤抑制因子、Rheb原癌基因、hVps34磷脂酰肌醇激酶和Rag GTP酶——决定肿瘤的生长、代谢和凋亡易感性。靶向mTOR和PI3K酶的新型化合物可能会进一步提高在多种人类疾病（尤其是癌症）中抑制该通路的疗效。
