University Campus Bio-Medico, Medical Oncology, via Alvaro del Portillo, 200, Rome, Italy.
Expert Opin Investig Drugs. 2011 Dec;20(12):1685-705. doi: 10.1517/13543784.2011.628984. Epub 2011 Oct 20.
Sarcomas are rare heterogeneous malignancies of mesenchymal origin relatively common during childhood. Disruption of the mammalian target of rapamycin (mTOR) pathway is a very common event during the tumorigenesis of several types of cancer. In particular, strong preclinical evidences suggest pivotal roles of this pathway during the sarcomagenesis. Therefore, the inhibition of mTOR via rapamycin, rapamycin analogs (rapalogs) and ATP-competitive inhibitors seems to be a promising path to follow for a fully tailored therapy.
The aim of the present review is to summarize the available data about the mechanisms of mTOR pathway, its biological implications and its possible role in the pathogenesis of soft tissue sarcoma. Moreover, preclinical and clinical evidences of different mTOR inhibitors in the treatment of sarcomas are reported.
Early studies with mTOR inhibitors have demonstrated promising antitumor activity in patients with metastatic sarcoma who have failed standard treatments: that is why mTOR inhibitors represents today a promising chance to improve the prognosis of those patients affected by these rare disease, which is today still extremely poor.
肉瘤是一种罕见的起源于间叶组织的异质性恶性肿瘤，在儿童中相对常见。哺乳动物雷帕霉素靶蛋白（mTOR）通路的破坏是多种癌症发生过程中的一个非常常见的事件。特别是，强有力的临床前证据表明该通路在肉瘤发生过程中起着关键作用。因此，通过雷帕霉素、雷帕霉素类似物（rapalogs）和 ATP 竞争性抑制剂抑制 mTOR，似乎是一种针对特定治疗的很有前途的途径。
本综述的目的是总结 mTOR 通路的机制、生物学意义及其在软组织肉瘤发病机制中的可能作用的现有数据。此外，还报告了不同 mTOR 抑制剂在肉瘤治疗中的临床前和临床证据。
早期的 mTOR 抑制剂研究表明，在标准治疗失败的转移性肉瘤患者中，这些抑制剂具有有前景的抗肿瘤活性：这就是为什么 mTOR 抑制剂代表了改善这些罕见疾病患者预后的一种很有前途的机会，这些患者的预后目前仍然极差。
