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Expert Opin Investig Drugs. 2013 Nov;22(11):1485-93. doi: 10.1517/13543784.2013.831404. Epub 2013 Aug 21.
The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway plays a critical role in controlling cellular metabolism, proliferation and cell cycle regulation. Constitutive activation of this pathway has been demonstrated in many tumor types. Targeting the PI3K/AKT/mTOR pathway is of increasing therapeutic interest.
Ridaforolimus belongs to a class of agents known as the rapalogs, first-generation mTOR inhibitors, which inhibit mTORC1, a part of the mTOR complex. Both oral and intravenous formulations of this agent have been tested in Phase II clinical trials for the treatment of solid tumors and hematologic malignancies. Promising results have been seen in endometrial cancer and soft tissue and bone sarcomas.
This article summarizes the current clinical and biological data on the use of ridaforolimus emerging from these Phase II studies, and provides potential advantages and drawbacks of the mTOR inhibitors in the current clinical practice.
PI3K/AKT/哺乳动物雷帕霉素靶蛋白（mTOR）途径在控制细胞代谢、增殖和细胞周期调节方面起着关键作用。许多肿瘤类型中都证实了该途径的组成性激活。针对 PI3K/AKT/mTOR 途径的治疗具有越来越大的治疗意义。
瑞戈非尼属于雷帕霉素类似物这一类药物，第一代 mTOR 抑制剂，可抑制 mTORC1，mTOR 复合物的一部分。该药物的口服和静脉制剂均已在 II 期临床试验中进行了测试，用于治疗实体瘤和血液恶性肿瘤。在子宫内膜癌和软组织及骨肉瘤中观察到了有前景的结果。
本文总结了这些 II 期研究中出现的关于瑞戈非尼使用的最新临床和生物学数据，并提供了当前临床实践中 mTOR 抑制剂的潜在优势和不足。
