Arduini Daniela, Ciccarese Chiara, Strusi Alessandro, Beccia Viria, Pedone Romina Rose, Scala Alessandro, Sardaro Valeria, Tortora Giampaolo, Iacovelli Roberto
Medical Oncology, Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, Rome, Italy.
Medical Oncology, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Curr Cancer Drug Targets. 2025 Jan 6. doi: 10.2174/0115680096323507241101064127.
Systemic therapy for metastatic Renal Cell Carcinoma (mRCC) has dramatical-ly improved in the last years because of the use of immunotherapy with checkpoint inhibi-tor combinations with or without targeted therapies against the Vascular Endothelial Growth Factor Receptors (VEGFR). As a result, patients with mRCC have prolonged sur-vival time, but they ultimately develop resistance and the disease progresses, which high-lights the critical need for novel treatment options. The Hypoxia-inducible Factor (HIF) pathway is central to the pathophysiology of ccRCC and von Hippel-Lindau (VHL) disease. As part of the VHL-HIF-VEGF axis, the HIF-2α inhibition has been identified as a rationale target for mRCC treatment. Indeed, one such agent called belzutifan is already approved for VHL-associated RCC and other VHL-associated neoplasms, and a series of trials have indicated encouraging efficacy and good tolerability in sporadic mRCC as well. The potential inclusion of belzutifan into the mRCC treatment armamentarium either as a single agent or as combination therapy could cover the lack of therapeutic options as well as the need for a new combination in mRCC; therefore, this drug has the potential to be largely used in mRCC. In this review, we have recapitulated the clinical data supporting the use of belzutifan in mRCC as monotherapy and the background for combination with other agents as well as its safety profile.
近年来，由于使用了免疫疗法联合或不联合针对血管内皮生长因子受体（VEGFR）的靶向疗法，转移性肾细胞癌（mRCC）的全身治疗有了显著改善。因此，mRCC患者的生存时间得以延长，但最终他们会产生耐药性，疾病会进展，这突出了对新型治疗方案的迫切需求。缺氧诱导因子（HIF）通路在透明细胞肾细胞癌（ccRCC）和冯·希佩尔-林道（VHL）病的病理生理学中至关重要。作为VHL-HIF-VEGF轴的一部分，HIF-2α抑制已被确定为mRCC治疗的合理靶点。事实上，一种名为belzutifan的药物已被批准用于治疗VHL相关肾细胞癌和其他VHL相关肿瘤，一系列试验也表明其在散发性mRCC中也具有令人鼓舞的疗效和良好的耐受性。将belzutifan作为单一药物或联合疗法纳入mRCC治疗方案中，既可以弥补治疗选择的不足，也满足了mRCC中新型联合治疗的需求；因此，这种药物有可能在mRCC中得到广泛应用。在本综述中，我们总结了支持belzutifan单药治疗mRCC的临床数据、与其他药物联合使用的背景及其安全性概况。
