HIF2α抑制剂在肾细胞癌中的研究进展

Research Progress on HIF2αInhibitors in Treatment of Renal Cell Carcinoma

肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)是肾细胞癌(renal cell carcinoma,RCC)中最常见的亚型,常伴有VHL(Von Hippel Lindau)基因突变。VHL突变使肿瘤更易转移和进展,患者预后较乳头状肾细胞癌(papillary renal cell carcinoma,pRCC)和嫌色细胞肾细胞癌(chromophobe renal cell carcinoma,chRCC)更差。尽管多种药物获批用于治疗ccRCC,但晚期ccRCC的5年生存率仅为20%左右。随着对肾细胞癌发生机制研究的深入,缺氧诱导因子HIF2α被认为是VHL下游的关键分子。HIF2α抑制剂能够抑制肿瘤增殖和血管生成,发挥抗肿瘤作用。近年来,多个评估HIF2α抑制剂安全性和疗效的临床试验正在开展。该文对HIF2α抑制剂的作用机制、临床试验内容及其结果进行了总结,探讨了HIF2α抑制剂在肾细胞癌治疗中的临床疗效和可能的发展方向。

Clear cell renal cell carcinoma(ccRCC)is the most common subtype of renal cell carcinoma(RCC),characterized by the mutation of VHL(Von Hippel Lindau)gene.The mutated VHL contributes to tumor progression and metastasis,culminating in a worse prognosis in ccRCC than in pRCC(papillary renal cell carcinoma)and chRCC(chromophobe renal cell carcinoma).Although multiple drugs have been approved to treat patients with terminal-stage ccRCC,the 5-year overall survival is only about 20%.With further study of the pathogenesis of renal cell carcinoma,hypoxia-inducing factor HIF2αis considered to be a key downstream molecule of VHL.HIF2αinhibitors can inhibit tumor proliferation and angiogenesis,and play an antitumor role.In recent years,several clinical trials evaluating the safety and efficacy of HIF2αinhibitors are under progress.In this paper,the mechanism of action,clinical trial content and results of HIF2αinhibitors are summarized,and the clinical efficacy and possible development direction of HIF2αinhibitors in the treatment of renal cell carcinoma are discussed.