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VHL and HIF signalling in renal cell carcinogenesis
Abstract
Hypoxia‐inducible factor (HIF) plays an important role in renal tumourigenesis. In the majority of clear cell RCC (ccRCC), the most frequent and highly vascularized RCC subtype, HIF is constitutively activated by inactivation of the von Hippel–Lindau gene. Of the HIF subunits, HIF‐2α appears to be more oncogenic than HIF‐1α, in that HIF‐2α activates pro‐tumourigenic target genes. In addition, recent studies indicate that HIF‐1α, more than HIF‐2α, can undergo proteasomal degradation in VHL − /− RCC cells. A more detailed understanding of the molecular basis of hypoxia and angiogenesis in renal carcinogenesis has set the stage for the development of targeted therapies, inhibiting multiple HIF‐related pathways, such as the phosphatidylinositol 3‐kinase–AKT–mTOR, RAS/RAF/MAP, and VEGF signalling routes. However, despite the positive results of these targeting agents in progression‐free survival, clinical resistance remains an issue. Recent pre‐clinical studies have suggested new targeting approaches such as inhibition of HIF‐driven key metabolic enzymes and have introduced new HIF targeting agents, such as histone deacetylase inhibitors, with successful anti‐neoplastic effects. In this review, we discuss existing and novel findings about RCC carcinogenesis, with subsequent clinical implications. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Cited by
Zhong, Q., Xiao, X., Qiu, Y., Xu, Z., Chen, C., Chong, B., Zhao, X., Hai, S., Li, S., An, Z., et al. (2023) · MedComm · doi:10.1002/mco2.261 · Cited by 442
Masiero, M., Simões, F. C., Han, H. D., Snell, C., Peterkin, T., Bridges, E., Mangala, L. S., Wu, S. Y.-Y., Pradeep, S., Li, D., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.06.004 · Cited by 313
Casillas, A. L., Chauhan, S. S., Toth, R. K., Sainz, A. G., Clements, A. N., Jensen, C. C., Langlais, P. R., Miranti, C. K., Cress, A. E., & Warfel, N. A. (2021) · Oncogene · doi:10.1038/s41388-021-01915-1 · Cited by 44
Shang, D., Xu, X., Wang, D., Li, Y., & Liu, Y. (2013) · World Journal of Urology · doi:10.1007/s00345-013-1077-4 · Cited by 12
Metadata
- Authors
- Baldewijns, M. M., van Vlodrop, I. J., Vermeulen, P. B., Soetekouw, P. M., van Engeland, M., & de Bruïne, A. P.
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2010-05-04
- Volume
- 221
- Issue
- 2
- Pages
- 125-138
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2143013757
- Cited by
- 316
- References
- 143
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
