Department of Oncology and Hematology, Hôpitaux Universitaires de Strasbourg, 1 Av Molière, 67098 Strasbourg, France.
Anticancer Res. 2012 Jul;32(7):2463-70.
The phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been identified as a key signaling pathway for important cellular functions such as growth control, metabolism and translation initiation. Several proteins within this pathway are valuable anticancer drug targets, among which several inhibitors of mTOR are now administered in routine practice. A better understanding of the structure and functions of PI3K has led to the development of novel inhibitors that have a more favorable toxicity profile as compared to the first generation of anti-PI3K drugs. In this article, we review the basics of PI3K biology and focus on its inhibitors, currently under investigation in clinical trials. The perspective for future directions in the setting of PI3K inhibition and novel trials is also discussed.
磷酸肌醇 3-激酶/蛋白激酶 B/雷帕霉素靶蛋白（PI3K/AKT/mTOR）途径已被确定为关键的信号通路，对于细胞的重要功能如生长控制、代谢和翻译起始具有重要作用。该通路中的几种蛋白是有价值的抗癌药物靶点，其中几种 mTOR 抑制剂目前已在常规实践中应用。对 PI3K 结构和功能的更深入了解导致了新型抑制剂的开发，与第一代抗 PI3K 药物相比，它们具有更有利的毒性特征。本文综述了 PI3K 生物学的基础知识，并重点介绍了目前正在临床试验中研究的其抑制剂。还讨论了在 PI3K 抑制和新型试验中未来的研究方向。
