Loss of Von Hippel–Lindau (VHL) Tumor Suppressor Gene Function: VHL–HIF Pathway and Advances in Treatments for Metastatic Renal Cell Carcinoma (RCC)

Renal cell carcinoma (RCC) is a malignancy of the kidney originating from the tubular epithelium. Inactivation of the von Hippel–Lindau tumor-suppressor gene (VHL) is found in most clear cell renal cell carcinomas (ccRCCs). The VHL–HIF–VEGF/VEGFR pathway, which involves the von Hippel–Lindau tumor s...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-09, Vol.22 (18), p.9795
Main Authors: Kim, Hyunho, Shim, Byoung Yong, Lee, Seung-Ju, Lee, Ji Youl, Lee, Hyo-Jin, Kim, In-Ho
Format: Article
Language:English
Subjects:
Angiogenesis
Antiangiogenic agents
Antiangiogenics
Cell division
Chromosomes
Clear cell-type renal cell carcinoma
Epithelium
Genes
Growth factors
HIF
Hypoxia
Hypoxia-inducible factors
immune checkpoint inhibitor
Immune checkpoint inhibitors
Immunomodulation
Kidney cancer
Malignancy
Metastases
Metastasis
Mutation
Patients
Proteins
Renal cell carcinoma
Review
tumor suppressor gene
Tumor suppressor genes
Tumorigenesis
Tumors
Vascular endothelial growth factor
Vascular endothelial growth factor receptors
VEGFR
VHL
VHL protein
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Summary:Renal cell carcinoma (RCC) is a malignancy of the kidney originating from the tubular epithelium. Inactivation of the von Hippel–Lindau tumor-suppressor gene (VHL) is found in most clear cell renal cell carcinomas (ccRCCs). The VHL–HIF–VEGF/VEGFR pathway, which involves the von Hippel–Lindau tumor suppressor protein (VHL), hypoxia-inducible factor (HIF), vascular endothelial growth factor (VEGF), and its receptor (VEGFR), is a well-studied therapeutic target for metastatic ccRCC. Therefore, over the past decade, anti-angiogenic agents targeting VEGFR have served as the standard treatment for metastatic RCC. Recently, based on the immunomodulatory effect of anti-VEGFR therapy, anti-angiogenic agents and immune checkpoint inhibitor combination strategies have also emerged as therapeutic strategies. These advances were made possible by the improved understanding of the VHL–HIF pathway. In this review, we summarize the historical evolution of ccRCC treatments, with a focus on the involvement of the VHL–HIF pathway.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22189795