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Published on: August 14, 2017
Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel-Lindau-Deficient Renal Cancer
Florinda Meléndez-Rodríguez1,2, Olga Roche3,4,5, Ricardo Sanchez-Prieto3,4,6
1Research Unit, Hospital of Santa Cristina, Research Institute Princesa (IP), Autonomous University of Madrid, Madrid, Spain.
Abstract:
The most common type of the renal cancers detected in humans is clear cell renal cell carcinomas (ccRCCs). These tumors are usually initiated by biallelic gene inactivation of the Von Hippel-Lindau (VHL) factor in the renal epithelium, which deregulates the hypoxia-inducible factors (HIFs) HIF1α and HIF2α, and provokes their constitutive activation irrespective of the cellular oxygen availability. While HIF1α can act as a ccRCC tumor suppressor, HIF2α has emerged as the key HIF isoform that is essential for ccRCC tumor progression. Indeed, preclinical and clinical data have shown that pharmacological inhibitors of HIF2α can efficiently combat ccRCC growth. In this review, we discuss the molecular basis underlying the oncogenic potential of HIF2α in ccRCC by focusing on those pathways primarily controlled by HIF2α that are thought to influence the progression of these tumors.
Insights
Clear cell renal cell carcinoma (ccRCC) growth is driven by HIF2α. Targeting HIF2α with drugs shows promise for treating this common kidney cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common human kidney cancer.
- ccRCC initiation involves Von Hippel-Lindau (VHL) gene inactivation, leading to deregulated hypoxia-inducible factors (HIFs).
- HIF1α acts as a tumor suppressor, while HIF2α is crucial for ccRCC progression.
Purpose of the Study:
- To review the molecular mechanisms behind HIF2α's oncogenic role in ccRCC.
- To highlight pathways regulated by HIF2α that drive ccRCC tumor progression.
Main Methods:
- Literature review of preclinical and clinical data.
- Focus on molecular pathways controlled by HIF2α.
Main Results:
- HIF2α is essential for ccRCC tumor progression.
- Pharmacological inhibition of HIF2α demonstrates efficacy in combating ccRCC growth.
Conclusions:
- Understanding HIF2α's molecular basis is key to developing effective ccRCC therapies.
- Targeting HIF2α represents a promising therapeutic strategy for ccRCC.
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