基于HIF-2α靶向治疗晚期透明细胞肾细胞癌的研究进展

Research Progress of HIF-2α-Targeted Therapy for Advanced Clear Cell Renal Cell Carcinoma

肾癌是泌尿系统肿瘤中的常见病,其中肾透明细胞癌占大多数。VHL基因的失活在肾癌中广泛存在,导致低氧诱导因子(hypoxia inducible factor-2α,HIF-2α)的泛素化降解障碍,进而引起血管内皮生长因子(vascular endotelial growth factor,VEGF)的过表达,促进了肿瘤发生。近些年,靶向HIF-2α的抑制剂作为治疗晚期透明细胞癌的药物进入临床。对VHL通路、HIF-2α抑制剂作用机理的研究进展和治疗效果进行了综述。

Kidney cancer is a common disease in urinary system tumors, in which renal clear cell carcinoma accounts for the majority. Inactivation of VHL gene is widespread in renal cell carcinoma, leading to less ubiquitination and degradation of hypoxia-inducible factor (hypoxia inducible factor -2α, HIF- 2α), which in turn causes high expression of Vascular endotelial growth factor (VEGF) to promote tumorigenesis. In recent years, inhibitors targeting HIF- 2α have entered the clinic as drugs for the treatment of advanced clear cell carcinoma. In this paper, the research progress and therapeutic effects of VHL pathway, HIF-2α inhibitor mechanism is briefly summarized.