Smolewski Piotr
Department of Hematology, Medical University of Lodz, Lodz, Poland.
Anticancer Drugs. 2006 Jun;17(5):487-94. doi: 10.1097/00001813-200606000-00001.
The mammalian target of rapamycin (mTOR) is a threonine kinase involved in intracellular pro-survival signaling. Its activation leads to progression from the G1 to S phase of the cell cycle. Constitutive activation of the mTOR-related messengers, including phosphatidylinositol 3-kinase, Akt kinase, ribosomal p70S6 kinase and eukaryotic translation initiation factor 4E-binding protein kinase, was found in numerous malignancies. Recent data indicate that the mTOR kinase pathway can be an attractive target for anti-cancer drug development. A well-known mTOR inhibitor is rapamycin (RAPA), previously applied as an immunosuppressive agent in transplant studies. Recently, analogs of RAPA, such as CCI-779, RAD001 and AP23573, have been developed. All of those agents are currently being tested in patients with solid or hematological tumors in several clinical trials. This review presents recent developments in targeting the mTOR kinase pathway.
雷帕霉素的哺乳动物靶点（mTOR）是一种参与细胞内促生存信号传导的苏氨酸激酶。其激活导致细胞周期从G1期进展到S期。在众多恶性肿瘤中发现了包括磷脂酰肌醇3激酶、Akt激酶、核糖体p70S6激酶和真核翻译起始因子4E结合蛋白激酶在内的mTOR相关信使分子的组成性激活。最近的数据表明，mTOR激酶途径可能是抗癌药物开发的一个有吸引力的靶点。一种著名的mTOR抑制剂是雷帕霉素（RAPA），它以前在移植研究中用作免疫抑制剂。最近，已开发出RAPA的类似物，如CCI-779、RAD001和AP23573。目前，所有这些药物都在多项临床试验中用于实体瘤或血液肿瘤患者的测试。本综述介绍了靶向mTOR激酶途径的最新进展。
