Targeting the HIF2-VEGF axis in renal cell carcinoma

被引：396

作者：

Choueiri, Toni K. ^{[1
,2
]}

Kaelin, William G., Jr. ^{[1
,2
,3
]}

机构：

[1] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

NATURE MEDICINE | 2020年 / 26卷 / 10期

基金：

英国科研创新办公室;

关键词：

ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR; HIPPEL-LINDAU-DISEASE; RANDOMIZED PHASE-II; PAS-B DOMAIN; DOUBLE-BLIND; INTERFERON-ALPHA; HIF-ALPHA; TUMOR SUPPRESSION; MAMMALIAN TARGET;

D O I：

10.1038/s41591-020-1093-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Anticancer therapies that target the HIF oxygen-sensing pathways are moving into the clinic, in particular in kidney cancer. 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 byVHLinactivation, such as clear-cell renal cell carcinoma (ccRCC). Multiple VEGF inhibitors are now approved for the treatment of ccRCC, and a HIF2 alpha 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 HIF2 alpha-targeted therapies for patients with VHL-associated tumors. We also present future directions for extending the use of these therapies to other cancers.

引用

页码：1519 / 1530

页数：12

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