以肝素酶为靶点的抗肿瘤药物研究进展

Research Advances of Anticancer Drug with Heparanase as a Target

恶性肿瘤一直以来都是全球范围内的热门课题,肿瘤细胞的恶性转移是肿瘤致死率居高不下的重要原因。研究发现,肝素酶(Heparanase,HPA)在肿瘤发展的过程中起关键作用,是抗肿瘤治疗的重要靶点;肝素酶抑制剂,通过降低HPA的活性或抑制HPA的表达,有效抑制肿瘤细胞的侵袭和迁移,是颇具潜力的抗肿瘤治疗药物。文章对HPA作为肿瘤治疗靶点以及针对该靶点的抗肿瘤新药研发进行了综述,重点介绍了具有干扰HPA活性的底物类似物——肝素衍生物SST0001和硫酸化寡糖PG545、小分子化合物,以及抑制HPA表达的小干扰RNA(siRNA)等,为设计合理、高效的肝素酶抑制剂提供参考。

Malignant cancer therapy has always been a hot topic in the worldwide,and malignant metastasis in tumor is an important reason for its high mortality rate.Heparanase has been proved to play a key role in the process of tumor development and becomes an important target for anti-cancer therapy.Heparanase inhibitors,effectively inhibiting tumor invasion and migration,are regarded as a potent anticancer drug by reducing the activity or inhibiting the expression of HPA.The development of new drugs based on HPA is reviewed in this article,highlighting those drugs which can decrease HPA activity including HPA substrate analogs heparin derivative SST0001 and sulfated oligosaccharide PG545,and small molecule compounds.Besides,small interfering RNA was also reviewed which can inhibit the the expression of HPA.The review can guide the rational design of heparanase inhibitors with high efficiency.