Oya Mototsugu
Department of Urology, Keio University School of Medicine.
Nihon Rinsho. 2010 Jun;68(6):1067-71.
Mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving proliferation, cell survival, and angiogenesis. These pathways are frequently abnormally regulated in cancer. Notably, Akt is an upstream molecule which is over-expressed and/or activated in several cancers. Therefore, mTOR inhibitors can be options for the treatment of cancers. At present, mTOR inhibitors are applied to treat patients with metastatic renal cell carcinoma (RCC). Temsirolimus is indicated as the first line therapy for RCC patients with poor prognosis, whereas everolimus as the second line for those refractory to sorafenib or sunitinib. Interstitial pneumonia is the most serious adverse event for both agents. Clinical trials are under way to explore indications for various cancers.
雷帕霉素哺乳动物靶点（mTOR）蛋白复合体作为各种涉及增殖、细胞存活和血管生成的细胞内信号通路的整合中心发挥作用。这些通路在癌症中经常受到异常调节。值得注意的是，Akt是一种上游分子，在几种癌症中过度表达和/或被激活。因此，mTOR抑制剂可作为癌症治疗的选择。目前，mTOR抑制剂被用于治疗转移性肾细胞癌（RCC）患者。替西罗莫司被指定为预后不良的RCC患者的一线治疗药物，而依维莫司则作为对索拉非尼或舒尼替尼耐药患者的二线治疗药物。间质性肺炎是这两种药物最严重的不良事件。目前正在进行临床试验以探索各种癌症的适应症。
