缺氧诱导因子
癌症研究
肾透明细胞癌
肾细胞癌
HIF1A型
医学
转录因子
免疫检查点
血管内皮生长因子
缺氧(环境)
血管内皮生长因子受体
癌症
肿瘤科
内科学
生物
免疫疗法
化学
生物化学
有机化学
氧气
基因
作者
Toni K. Choueiri,William G. Kaelin
出处
期刊:Nature Medicine
[Springer Nature]
日期:2020-10-01
卷期号:26 (10): 1519-1530
被引量:312
标识
DOI:10.1038/s41591-020-1093-z
摘要
Insights into the role of the tumor suppressor pVHL in oxygen sensing motivated the testing of drugs that target the transcription factor HIF or HIF-responsive growth factors, such as VEGF, for the treatment of cancers caused by VHL inactivation, such as clear-cell renal cell carcinoma (ccRCC). Multiple VEGF inhibitors are now approved for the treatment of ccRCC, and a HIF2α inhibitor has advanced to phase 3 development for this disease. These inhibitors are now also increasingly combined with immune-checkpoint blockers. In this Perspective, we describe the understanding of the mechanisms of oxygen sensing and hypoxia signaling that resulted in the development of HIF2α-targeted therapies for patients with VHL-associated tumors. We also present future directions for extending the use of these therapies to other cancers.
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