新型分子靶向抗癌药物-PI3K抑制剂

摘要

Molecular-targeted antitumor drugs are new type of antitumor drugs which target molecules specially existing in tumor cells and therefore inhibit proliferation,invasion,or metastasis of tumor cells with little side effect on normal cells.Phosphatidylinositol 3-kinase (PI3K),which promotes cell survival,proliferation and migration via activating the downstream AKT,is known to be closely involved in tumorigenesis.The development of PI3K inhibitor has therefore attracted high attention from pharmaceutical industries.Up to 20 compounds are now under evaluation in clinical trials.Our paper reviews the well reported PI3K inhibitors as well as their combination with other antitumor drugs after a brief introduction about PI3K.%分子靶向抗癌药物是指作用于肿瘤细胞的特定分子靶点,抑制肿瘤细胞的增殖、侵袭、转移等恶性生物行为,从而产生抗肿瘤作用的药物.PI3K(磷脂酰肌醇3-激酶)为一种由调节亚单位p85或p101和催化亚单位p110组成的脂激酶,通过激活下游的AKT等促进细胞生存、增殖和迁移等.由于PI3K在癌症发生中所起的关键作用,开发以PI3K为靶标的抑制剂引起制药界的高度重视.自2006年第一个新型PI3K抑制剂NVP-BEZ235开始临床试验以来,迄今已有近20个化合物进入临床试验阶段.本文首先简介PI3K的功能和分类,然后就PI3K抑制剂的研究进展以及与其它抗癌药物的联合用药做一综述.