PI3K/Akt信号通路及其抑制剂的研究进展(1)
摘 要：磷脂酰肌醇3激酶(PI3K)/丝氨酸-苏氨酸激酶(Akt)信号通路在信号转导的调控中扮演着重要角色，能调节细胞增殖、凋亡、代谢、运动、血管生成等生物过程。与其他信号通路相比，PI3K/Akt信号通路的组成部分更庞大，在肿瘤中更多见。目前已证实多种肿瘤中存在PI3K/Akt信号通路的超活化，对肿瘤细胞的存活、生长、运动、血管生成和代谢意义重大。因此，抑制PI3K和与通路相关的成分可能会使肿瘤生长受抑，使患者预后改善。PI3K/Akt信号通路抑制剂包括针对单一成分的抑制剂和双重抑制剂。目前大量的PI3K抑制剂已在临床前期研究中取得良好结果，有些已经在血液恶性肿瘤和实体肿瘤中进行了临床试验。在此综述中，我们简单的总结了PI3K-AKt通路的研究成果，讨论了PI3K抑制剂从临床前研究到临床研究的发展前景。
关键词：PI3K；Akt；mTOR；PI3K/Akt信号通路抑制剂
中图分类号：R34 文献标识码：A DOI：10.3969/j.issn.1006-1959.2018.10.011
, 百拇医药
文章编号：1006-1959(2018)10-0034-03
Research Progress of PI3K/Akt Signaling Pathway and its Inhibitors
WANG Meng-hua1，LU Jun-kun2
(1.Jiamusi University，Jiamusi 154003，Heilongjiang，China；
2.The First Affiliated Hospital of Jiamusi University，Jiamusi 154003，Heilongjiang，China)
Abstract：The phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt)signaling pathway plays an important role in the regulation of signal transduction，and can regulate biological processes such as cell proliferation，apoptosis，metabolism，movement，and angiogenesis.Compared with other signaling pathways，the components of the PI3K/Akt signaling pathway are larger and more common in tumors.It has been confirmed that there are hyperactivations of PI3K/Akt signaling pathways in many types of tumors，which are important for the survival，growth，movement，angiogenesis and metabolism of tumor cells.Therefore，inhibition of PI3K and pathway-related components may inhibit tumor growth and improve patient outcomes.PI3K/Akt signaling pathway inhibitors include single-component inhibitors and dual inhibitors.A large number of PI3K inhibitors have achieved good results in preclinical studies，and some have been clinically tested in hematologic malignancies and solid tumors.In this review，we briefly summarized the research results of the PI3K-AKt pathway and discussed the prospects for the development of PI3K inhibitors from preclinical studies to clinical studies.
, http://www.100md.com
Key words：PI3K；Akt；mTOR；PI3K/Akt signaling pathway inhibitors
PI3K/Akt信號通路是细胞内信号传导通路，对细胞凋亡、恶变、肿瘤进展、转移和放射治疗都有重要作用[1]，可因突变、扩增、缺失、甲基化和翻译后的修饰，导致它在癌症患者中调节异常。常因基因突变和复制数变异(CNAs)被激活。PI3K的催化亚基p110α是肿瘤细胞增殖、迁移和入侵所必需的，而p110β则是细胞存活和肿瘤生成的关键[2]。因此，PI3K抑制剂以及与该通路相关的其他成分的抑制剂，正在被积极地用于癌症靶向治疗。
由于PI3K/Akt通路在癌症研究中的重要性和价值性，近年来针对这一信号通路研究开发了一系列的抑制剂，如PI3K抑制剂LY294002、Akt抑制剂P529、mTOR抑制剂雷帕霉素、双重PI3K /mTOR抑制剂BEZ235。目前已经设计了50多种PI3K抑制剂用于治疗癌症。然而，只有少数的几种已经成功地进入了临床试验。在此，我们总结了PI3K/Akt通路的研究成果，重点介绍了其组成成分，即PI3K和Akt，分析了PI3K抑制剂用于癌症治疗的可能性，从而肯定了PI3K抑制剂对癌症治疗的意义。, http://www.100md.com(王梦华 卢均坤)
关键词：PI3K；Akt；mTOR；PI3K/Akt信号通路抑制剂
中图分类号：R34 文献标识码：A DOI：10.3969/j.issn.1006-1959.2018.10.011
, 百拇医药
文章编号：1006-1959(2018)10-0034-03
Research Progress of PI3K/Akt Signaling Pathway and its Inhibitors
WANG Meng-hua1，LU Jun-kun2
(1.Jiamusi University，Jiamusi 154003，Heilongjiang，China；
2.The First Affiliated Hospital of Jiamusi University，Jiamusi 154003，Heilongjiang，China)
Abstract：The phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt)signaling pathway plays an important role in the regulation of signal transduction，and can regulate biological processes such as cell proliferation，apoptosis，metabolism，movement，and angiogenesis.Compared with other signaling pathways，the components of the PI3K/Akt signaling pathway are larger and more common in tumors.It has been confirmed that there are hyperactivations of PI3K/Akt signaling pathways in many types of tumors，which are important for the survival，growth，movement，angiogenesis and metabolism of tumor cells.Therefore，inhibition of PI3K and pathway-related components may inhibit tumor growth and improve patient outcomes.PI3K/Akt signaling pathway inhibitors include single-component inhibitors and dual inhibitors.A large number of PI3K inhibitors have achieved good results in preclinical studies，and some have been clinically tested in hematologic malignancies and solid tumors.In this review，we briefly summarized the research results of the PI3K-AKt pathway and discussed the prospects for the development of PI3K inhibitors from preclinical studies to clinical studies.
, http://www.100md.com
Key words：PI3K；Akt；mTOR；PI3K/Akt signaling pathway inhibitors
PI3K/Akt信號通路是细胞内信号传导通路，对细胞凋亡、恶变、肿瘤进展、转移和放射治疗都有重要作用[1]，可因突变、扩增、缺失、甲基化和翻译后的修饰，导致它在癌症患者中调节异常。常因基因突变和复制数变异(CNAs)被激活。PI3K的催化亚基p110α是肿瘤细胞增殖、迁移和入侵所必需的，而p110β则是细胞存活和肿瘤生成的关键[2]。因此，PI3K抑制剂以及与该通路相关的其他成分的抑制剂，正在被积极地用于癌症靶向治疗。
由于PI3K/Akt通路在癌症研究中的重要性和价值性，近年来针对这一信号通路研究开发了一系列的抑制剂，如PI3K抑制剂LY294002、Akt抑制剂P529、mTOR抑制剂雷帕霉素、双重PI3K /mTOR抑制剂BEZ235。目前已经设计了50多种PI3K抑制剂用于治疗癌症。然而，只有少数的几种已经成功地进入了临床试验。在此，我们总结了PI3K/Akt通路的研究成果，重点介绍了其组成成分，即PI3K和Akt，分析了PI3K抑制剂用于癌症治疗的可能性，从而肯定了PI3K抑制剂对癌症治疗的意义。, http://www.100md.com(王梦华 卢均坤)