Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy.
Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy.
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DOI：
10.1158/1535-7163.mct-08-0801
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发表时间：
2009-01
影响因子：
5.7
通讯作者：
Powis G
中科院分区：
文献类型：
--
作者：
Ihle NT;Powis G
磷脂酰肌醇-3-激酶/ Akt信号通路是目前肿瘤学中最令人兴奋的药物靶点之一。然而，就在不久之前，由于对生理信号的影响，针对四种PI3K类1亚型的药物毒性太大，无法用于癌症治疗。从那时起，研究已经描述了这四种异构体在非病理性信号传导中的作用以及它们在癌症中的作用。人们已经在开发抑制一种或多种PI3K亚型以及与癌症密切相关的蛋白质的药物方面付出了广泛的努力。在动物实验中，这些药物已被证明具有耐受性和治疗效果，其中一些正在进行临床试验。本文综述了这些药剂的性质及其分子靶点。
The phosphatidylinositol-3-kinase / Akt signaling pathway is currently one of the most exciting drug targets in oncology. However only a short time ago, the paradigm existed that drugs targeted to the four PI3K class 1 isoforms would be too toxic for use in cancer therapy due to effects on physiological signaling. Since that time studies have delineated the roles of these four isoforms in non-pathological signaling as well as their roles in cancer. An extensive effort has gone into developing agents that inhibit one or more PI3K isoforms, as well as closely related proteins implicated in cancer. These agents have proven to be tolerable and therapeutically beneficial in animal studies, and a number are in clinical testing. The agents, their properties and their molecular targets are discussed in this review.