Brachmann Saskia, Fritsch Christine, Maira Saveur-Michel, García-Echeverría Carlos
Oncology Drug Discovery, Novartis Institutes of Biomedical Research, Basel, Switzerland.
Curr Opin Cell Biol. 2009 Apr;21(2):194-8. doi: 10.1016/j.ceb.2008.12.011. Epub 2009 Feb 7.
Epidemiological and experimental studies support an important role of the phosphoinosite 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway in the biology of human cancers. Over the past few years a number of components of this signaling cascade have been the subject of intense drug discovery activities. This article summarizes progress made in the identification of kinase inhibitors of PI3K and mTOR, with an emphasis placed on drugs currently undergoing clinical trials. Potential combination strategies, safety concerns, and resistance mechanisms for this new generation of anticancer agents are also discussed.
流行病学和实验研究支持磷酸肌醇3激酶（PI3K）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路在人类癌症生物学中发挥重要作用。在过去几年中，该信号级联反应的多个组分一直是药物研发活动的重点研究对象。本文总结了在PI3K和mTOR激酶抑制剂鉴定方面取得的进展，重点介绍了目前正在进行临床试验的药物。还讨论了新一代抗癌药物的潜在联合策略、安全性问题及耐药机制。
