2021年8月FDA批准低氧诱导因子-2α (HIF-2α)抑制剂Welireg(belzutifan)上市，用于治疗希佩尔·林道综合征 ( von Hippel-Lindau，VHL) 疾病相关癌症，包括：肾细胞癌(RCC)、中枢神经系统(CNS)血管母细胞瘤或胰腺神经内分泌肿瘤(pNET)，这些患者不需要立即手术。

2021年11月24日 · In this phase 2, open-label, single-group trial, we investigated the efficacy and safety of the HIF-2α inhibitor belzutifan (MK-6482, previously called PT2977), administered orally at a dose of 120...

von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary disorder characterized by retinal and CNS hemangioblastomas, pheochromocytoma, and clear cell renal cell carcinoma. With the discovery of the underlying gene linked to this disorder, the VHL gene, a revolution in clear cell RCC cancer biology has followed.

2023年4月17日 · In this study, our VHL-deleted RCC models reveal a novel metastatic mechanism that relies on cooperative interactions between two distinct populations of tumor cells: VHL-KO (VHL −) and...

Affected individuals are at increased risk of developing recurrent and bilateral kidney cysts and dysplastic lesions which may progress to clear cell renal cell carcinoma (ccRCC). Following the eponymous VHL gene inactivation, ccRCCs evolve through additional genetic alterations, resulting in both intratumor and intertumor heterogeneity.

The VHL gene protein has multiple functions that are linked to tumor suppression, but the best recognized and evidently linked to the development of renal cell carcinoma (RCC) is inhibition of hypoxia-inducible factor (HIF), as well as plays a role in …

2019年3月19日 · Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. Resistance to therapies targeting tumor angiogenesis...

2020年8月17日 · Mutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1α and HIF-2α transcription factors.

2016年9月1日 · Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all RCC and the Von Hippel–Lindau (VHL) tumor suppressor gene is mutated, deleted or epigenetically silenced in ∼85% of sporadic ccRCC [2]. The loss of VHL function leads to a constitutionally active hypoxia-inducible factor (HIF) pathway.

2024年7月19日 · Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples.