靶向 HIF-2α:belzutifan 在透明细胞肾癌治疗中的作用。

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Alejandro Valdés, Gonzalo Pizarro, Jaime González-Montero, Carlos Rojas, Mauricio Burotto
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引用次数: 0

摘要

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Targeting HIF-2α: the role of belzutifan in clear cell renal carcinoma management.

Introduction: Belzutifan is a first-in-class hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor. It targets the von Hippel-Lindau protein (pVHL)-HIF-vascular endothelial growth factor (VEGF) pathway, which is crucial in cellular responses to hypoxia. By inhibiting HIF-2α, belzutifan disrupts the transcription of genes involved in tumor growth and angiogenesis.

Areas covered: In this review, we describe the pVHL-HIF-VEGF pathway and how it led to the development of HIF inhibitors, including belzutifan. A search was conducted for trials involving Belzutifan, including phase I-III trials. We describe the relevant toxicity, with emphasis on hypoxia and anemia.

Expert opinion: Belzutifan is a relatively safe drug, with manageable adverse events, including anemia and hypoxia as on-target toxicity. Ongoing trials are studying its benefit in overall survival for RCC in first-line treatment and its potential in other malignancies. The LITESPARK-005 trial reported the benefit of belzutifan in progression-free survival (PFS) compared to everolimus in later lines of treatment, with improvement in quality-of-life outcomes. Given its different mechanism of action to currently available treatments, belzutifan is expected to play a prominent role in the treatment of clear cell renal carcinoma and other cancers.

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来源期刊
Expert Review of Clinical Pharmacology
Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.30
自引率
2.30%
发文量
127
期刊介绍: Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.
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