Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Brigham and Women's Hospital, Harvard Medical School; Howard Hughes Medical Institute.
Hematol Oncol Clin North Am. 2023 Oct;37(5):809-825. doi: 10.1016/j.hoc.2023.04.011. Epub 2023 Jun 1.
The most common form of kidney cancer is clear cell renal cell carcinoma (ccRCC). Biallelic VHL tumor suppressor gene inactivation is the usual initiating event in both hereditary (VHL Disease) and sporadic ccRCCs. The VHL protein, pVHL, earmarks the alpha subunits of the HIF transcription factor for destruction in an oxygen-dependent manner. Deregulation of HIF2 drives ccRCC pathogenesis. Drugs inhibiting the HIF2-responsive growth factor VEGF are now mainstays of ccRCC treatment. A first-in-class allosteric HIF2 inhibitor was recently approved for treating VHL Disease-associated neoplasms and appears active against sporadic ccRCC in early clinical trials.
最常见的肾癌类型是肾透明细胞癌（ccRCC）。VHL 抑癌基因的双等位基因失活是遗传性（VHL 病）和散发性 ccRCC 的常见起始事件。VHL 蛋白 pVHL 以氧依赖的方式标记 HIF 转录因子的α亚基进行降解。HIF2 的失调驱动 ccRCC 的发病机制。抑制 HIF2 反应性生长因子 VEGF 的药物现已成为 ccRCC 治疗的主要方法。最近批准了一种新型的别构 HIF2 抑制剂用于治疗 VHL 病相关肿瘤，并在早期临床试验中对散发性 ccRCC 表现出活性。
