VHL, the story of a tumour suppressor gene
Lucy Gossage1, Tim Eisen2, Eamonn R Maher3
11] Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [2] Department of Oncology, University of Cambridge, Box 193, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK. [3] Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
Abstract:
Since the Von Hippel-Lindau (VHL) disease tumour suppressor gene VHL was identified in 1993 as the genetic basis for a rare disorder, it has proved to be of wide medical and scientific interest. VHL tumour suppressor protein (pVHL) plays a key part in cellular oxygen sensing by targeting hypoxia-inducible factors for ubiquitylation and proteasomal degradation. Early inactivation of VHL is commonly seen in clear-cell renal cell carcinoma (ccRCC), and insights gained from the functional analysis of pVHL have provided the foundation for the routine treatment of advanced-stage ccRCC with novel targeted therapies. However, recent sequencing studies have identified additional driver genes that are involved in the pathogenesis of ccRCC. As our understanding of the importance of VHL matures, it is timely to review progress from its initial description to current knowledge of VHL biology, as well as future prospects for novel medical treatments for VHL disease and ccRCC.
Insights
The Von Hippel-Lindau (VHL) tumor suppressor gene VHL and its protein pVHL are crucial for oxygen sensing and clear-cell renal cell carcinoma (ccRCC) development. Understanding VHL biology advances treatments for VHL disease and ccRCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The Von Hippel-Lindau (VHL) gene, identified in 1993, is the genetic basis for VHL disease.
- The VHL tumor suppressor protein (pVHL) is integral to cellular oxygen sensing.
- pVHL targets hypoxia-inducible factors for degradation, a process critical in cellular function.
Purpose of the Study:
- To review the progress in understanding VHL gene and pVHL protein biology.
- To discuss the role of VHL in clear-cell renal cell carcinoma (ccRCC) pathogenesis.
- To explore future therapeutic strategies for VHL disease and ccRCC.
Main Methods:
- Literature review of VHL gene and protein function.
- Analysis of VHL's role in ccRCC development.
- Examination of current and emerging targeted therapies.
Main Results:
- VHL inactivation is common in ccRCC, leading to targeted therapies.
- pVHL's oxygen-sensing role is well-established.
- Recent studies reveal additional driver genes in ccRCC pathogenesis.
Conclusions:
- Continued research into VHL biology is essential for advancing medical treatments.
- Targeted therapies based on VHL pathway insights are improving ccRCC patient outcomes.
- Further investigation into VHL and other ccRCC driver genes holds promise for novel therapeutic development.
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