Hedgehog通路抑制剂靶向治疗肿瘤的研究进展

Research progress on targeted therapy of tumor with Hedgehog pathway inhibitors

Hedgehog(Hh)通路是人体内一条重要的信号通路,在胚胎发育和组织形成中起关键作用。Hh通路通过突变或者其他途径的异常激活与多种实体恶性肿瘤的发生发展密切相关。其中SMO受体是Hh信号通路中重要的调节靶点。Vismodegib和Sonidegib作为有效的SMO受体抑制剂,已被美国食品和药物管理局(FDA)批准用于治疗局部晚期或转移性基底细胞癌。随着研究者对Hh信号通路的不断探索,针对SMO受体上游或下游的靶向蛋白的抑制剂的研究也在如火如荼地开展。本文针对SMO抑制剂、SMO上游组分抑制剂和SMO下游组分抑制剂的研发进展进行了综述。

Hedgehog(Hh) signaling pathway is vital in human body, which plays a key role in embryonic development and tissue formation. The abnormal activation of Hh pathway is closely related to the occurrence and development of solid malignant tumors through mutation or other pathways. SMO receptor, named smoothened receptor, is a key point of Hh signaling pathway. Therefore, targeted inhibition of SMO receptor has become a research epicenter in the treatment of tumors. Vismodegib and Sonidegib, as the effctive SMO receptor inhibitors, were approved by the United States Food and Drug Administration(FDA) in order to healing locally advanced or metastatic basal cell carcinoma. With the continuous exploration of Hh signaling pathway, the inhibitors of SMO upstream or downstream receptors are also understood. The aim of the present paper was to summarize the research progress of SMO inhibitors, SMO upstream component inhibitors and SMO downstream component inhibitors.