鞘氨醇激酶2在肿瘤中的作用及其抑制剂研究进展

Advances in understanding the role of sphingosine kinase-2 in tumorigenesis and its inhibitors

近年来,鞘脂通路中的关键靶点鞘氨醇激酶2(sphingosine kinase 2,SphK2)在肿瘤发生发展过程中的作用逐渐被阐明。SphK2抑制剂既可单独作为抗癌药物,还可以与现有药物联合用药,以增加耐药肿瘤的治疗敏感性。其中SphK2选择性抑制剂ABC294640具有出色的口服生物利用度和体内分布,目前已进入临床Ⅱ期研究。基于该靶点进行创新药物开发具有很大的发展空间和应用前景,本文对近年来SphK2参与肿瘤发生发展的机制及SphK2抑制剂的开发现状进行综述。

In recent years the role of sphingosine kinase 2(SphK2),a key enzyme in the sphingolipid pathway,in the process of tumorigenesis has gradually been elucidated.Recent research has shown that SphK2 inhibitors can be used as anticancer drugs alone or in combination with existing drugs to increase the therapeutic sensitivity of drug-resistant tumors.Among them,one selective SphK2 inhibitor,ABC294640,shows excellent oral bioavailability and biodistribution in vivo and has now entered Phase II clinical research.Therefore,developing innovative drugs based on SphK2 is of great interest.Herein,we discuss progress in understanding the role of SphK2 in tumorigenesis and review the recent development of inhibitors of SphK2.