Division of Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi n. 53, 00144 Rome, Italy.
Curr Cancer Drug Targets. 2010 Aug;10(5):484-95. doi: 10.2174/156800910791517172.
Mammalian target of rapamycin (mTOR) is a key protein kinase controlling signal transduction from various growth factors and upstream proteins to the level of mRNA translation and ribosome biogenesis, with pivotal regulatory effects on cell cycle progression, cellular proliferation and growth, autophagy and angiogenesis. The mTOR pathway, and its upstream regulators in the PI3K/PTEN/AKT cascade, are altered in a variety of experimental and human malignancies.This has led to the prediction that mTOR inhibitors may be used as anticancer agents. With the recent approval of two mTOR-targeted drugs (temsirolimus and everolimus) for the treatment of renal cell carcinoma and mantle cell lymphoma, this paradigm has been effectively translated into the clinical setting. In this review, we discuss mTOR biology and regulation, the mode of action of mTOR inhibitors as anti-cancer agents, and current clinical evidence supporting the use of rapamycin-like mTOR inhibitors in cancer treatment.
哺乳动物雷帕霉素靶蛋白（mTOR）是一种关键的蛋白激酶，可控制各种生长因子和上游蛋白向 mRNA 翻译和核糖体生物发生水平的信号转导，对细胞周期进程、细胞增殖和生长、自噬和血管生成具有关键的调节作用。mTOR 通路及其上游 PI3K/PTEN/AKT 级联中的调节因子在各种实验性和人类恶性肿瘤中发生改变。这导致了这样的预测，即 mTOR 抑制剂可能被用作抗癌药物。随着最近批准两种 mTOR 靶向药物（替西罗莫司和依维莫司）用于治疗肾细胞癌和套细胞淋巴瘤，这一范例已有效地转化为临床实践。在这篇综述中，我们讨论了 mTOR 的生物学和调节、mTOR 抑制剂作为抗癌药物的作用模式，以及支持在癌症治疗中使用雷帕霉素样 mTOR 抑制剂的现有临床证据。
