靶向 HIF-2α 和贫血：透明细胞肾细胞癌的治疗突破。
Targeting HIF-2α and anemia: A therapeutic breakthrough for clear-cell renal cell carcinoma.
发表日期：2024 Jul 17
作者：
Patricia Rioja, M Rey-Cardenas, Guillermo De Velasco
来源：
CANCER TREATMENT REVIEWS
摘要：
肾细胞癌（RCC）是一种异质性疾病，其发病率在世界范围内不断增加。对 Von Hipple Lindau (VHP) 在调节缺氧诱导因子信号通路中的作用的识别和理解彻底改变了这种疾病的治疗。 Belzutifan 是一种口服缺氧诱导因子 (HIF)-2α 抑制剂，已证明可有效治疗 von Hippel-Lindau (VHL) 病以及治疗 PD-1/PD-L1- 治疗后疾病进展的成人肾细胞癌 (RCC)。和 VEGFR 靶向治疗。这种药物最常见的不良反应之一是贫血。然而，其治疗方法尚不为人所知。本综述总结了 VHL-HIF 通路在 ccRCC 中的作用，引起了人们对针对 HIF 活性的兴趣、belzutifan 的开发历史及其与贫血的关系，并提出了一种管理算法。版权所有 © 2024 Elsevier Ltd。保留所有权利。
Renal cell carcinoma (RCC) is a heterogenous disease which the incidence is increasing worldwide. The identification and understanding of the role of the Von Hipple Lindau (VHP) in regulating the hypoxia-inducible factor signaling pathway has revolutionized the treatment of this disease. Belzutifan is an oral hypoxia-inducible factor (HIF)-2α inhibitor, which has demonstrated efficacy in treating von Hippel-Lindau (VHL) disease and for the treatment of adults with RCC who experienced disease progression after PD-1/PD-L1- and VEGFR-targeted therapies. One of the most common adverse effect of this drug is anemia; however, it is treatment is not well known. This review summarizes role of the VHL-HIF pathway in ccRCC aroused the interest of targeting HIF activity, the history of belzutifan development and their relationship to anemia as well as propose a management algorithm.Copyright © 2024 Elsevier Ltd. All rights reserved.