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Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma
Fumarate hydratase (FH) - deficient renal cell carcinoma (FHdRCC) is a rare aggressive subtype of RCC caused by a germline or sporadic loss-of-function mutation in the FH gene. Here, we summarize how FH deficiency results in the accumulation of fumarate, which in turn leads to activation of hypoxia-...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337267/ https://www.ncbi.nlm.nih.gov/pubmed/35912170 http://dx.doi.org/10.3389/fonc.2022.906014 |
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author | Lindner, Andrea Katharina Tulchiner, Gennadi Seeber, Andreas Siska, Peter J. Thurnher, Martin Pichler, Renate |
author_facet | Lindner, Andrea Katharina Tulchiner, Gennadi Seeber, Andreas Siska, Peter J. Thurnher, Martin Pichler, Renate |
author_sort | Lindner, Andrea Katharina |
collection | PubMed |
description | Fumarate hydratase (FH) - deficient renal cell carcinoma (FHdRCC) is a rare aggressive subtype of RCC caused by a germline or sporadic loss-of-function mutation in the FH gene. Here, we summarize how FH deficiency results in the accumulation of fumarate, which in turn leads to activation of hypoxia-inducible factor (HIF) through inhibition of prolyl hydroxylases. HIF promotes tumorigenesis by orchestrating a metabolic switch to glycolysis even under normoxia, a phenomenon well-known as the Warburg effect. HIF activates the transcription of many genes, including vascular endothelial growth factor (VEGF). Crosstalk between HIF and epidermal growth factor receptor (EGFR) has also been described as a tumor-promoting mechanism. In this review we discuss therapeutic options for FHdRCC with a focus on anti-angiogenesis and EGFR-blockade. We also address potential targets that arise within the metabolic escape routes taken by FH-deficient cells for cell growth and survival. |
format | Online Article Text |
id | pubmed-9337267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93372672022-07-30 Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma Lindner, Andrea Katharina Tulchiner, Gennadi Seeber, Andreas Siska, Peter J. Thurnher, Martin Pichler, Renate Front Oncol Oncology Fumarate hydratase (FH) - deficient renal cell carcinoma (FHdRCC) is a rare aggressive subtype of RCC caused by a germline or sporadic loss-of-function mutation in the FH gene. Here, we summarize how FH deficiency results in the accumulation of fumarate, which in turn leads to activation of hypoxia-inducible factor (HIF) through inhibition of prolyl hydroxylases. HIF promotes tumorigenesis by orchestrating a metabolic switch to glycolysis even under normoxia, a phenomenon well-known as the Warburg effect. HIF activates the transcription of many genes, including vascular endothelial growth factor (VEGF). Crosstalk between HIF and epidermal growth factor receptor (EGFR) has also been described as a tumor-promoting mechanism. In this review we discuss therapeutic options for FHdRCC with a focus on anti-angiogenesis and EGFR-blockade. We also address potential targets that arise within the metabolic escape routes taken by FH-deficient cells for cell growth and survival. Frontiers Media S.A. 2022-07-15 /pmc/articles/PMC9337267/ /pubmed/35912170 http://dx.doi.org/10.3389/fonc.2022.906014 Text en Copyright © 2022 Lindner, Tulchiner, Seeber, Siska, Thurnher and Pichler https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Lindner, Andrea Katharina Tulchiner, Gennadi Seeber, Andreas Siska, Peter J. Thurnher, Martin Pichler, Renate Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma |
title | Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma |
title_full | Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma |
title_fullStr | Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma |
title_full_unstemmed | Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma |
title_short | Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma |
title_sort | targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337267/ https://www.ncbi.nlm.nih.gov/pubmed/35912170 http://dx.doi.org/10.3389/fonc.2022.906014 |
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