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Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers
Rare but recurrent mutations in the fibroblast growth factor receptor (FGFR) pathways, most commonly in one of the four FGFR receptor tyrosine kinase genes, can potentially be targeted with broad-spectrum multi-kinase or FGFR selective inhibitors. The complete spectrum of these mutations in paediatr...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244177/ https://www.ncbi.nlm.nih.gov/pubmed/37130917 http://dx.doi.org/10.1038/s41388-023-02705-7 |
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author | Brown, Lauren M. Ekert, Paul G. Fleuren, Emmy D. G. |
author_facet | Brown, Lauren M. Ekert, Paul G. Fleuren, Emmy D. G. |
author_sort | Brown, Lauren M. |
collection | PubMed |
description | Rare but recurrent mutations in the fibroblast growth factor receptor (FGFR) pathways, most commonly in one of the four FGFR receptor tyrosine kinase genes, can potentially be targeted with broad-spectrum multi-kinase or FGFR selective inhibitors. The complete spectrum of these mutations in paediatric cancers is emerging as precision medicine programs perform comprehensive sequencing of individual tumours. Identification of patients most likely to benefit from FGFR inhibition currently rests on identifying activating FGFR mutations, gene fusions, or gene amplification events. However, the expanding use of transcriptome sequencing (RNAseq) has identified that many tumours overexpress FGFRs, in the absence of any genomic aberration. The challenge now presented is to determine when this indicates true FGFR oncogenic activity. Under-appreciated mechanisms of FGFR pathway activation, including alternate FGFR transcript expression and concomitant FGFR and FGF ligand expression, may mark those tumours where FGFR overexpression is indicative of a dependence on FGFR signalling. In this review, we provide a comprehensive and mechanistic overview of FGFR pathway aberrations and their functional consequences in paediatric cancer. We explore how FGFR over expression might be associated with true receptor activation. Further, we discuss the therapeutic implications of these aberrations in the paediatric setting and outline current and emerging therapeutic strategies to treat paediatric patients with FGFR-driven cancers. [Image: see text] |
format | Online Article Text |
id | pubmed-10244177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102441772023-06-08 Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers Brown, Lauren M. Ekert, Paul G. Fleuren, Emmy D. G. Oncogene Review Article Rare but recurrent mutations in the fibroblast growth factor receptor (FGFR) pathways, most commonly in one of the four FGFR receptor tyrosine kinase genes, can potentially be targeted with broad-spectrum multi-kinase or FGFR selective inhibitors. The complete spectrum of these mutations in paediatric cancers is emerging as precision medicine programs perform comprehensive sequencing of individual tumours. Identification of patients most likely to benefit from FGFR inhibition currently rests on identifying activating FGFR mutations, gene fusions, or gene amplification events. However, the expanding use of transcriptome sequencing (RNAseq) has identified that many tumours overexpress FGFRs, in the absence of any genomic aberration. The challenge now presented is to determine when this indicates true FGFR oncogenic activity. Under-appreciated mechanisms of FGFR pathway activation, including alternate FGFR transcript expression and concomitant FGFR and FGF ligand expression, may mark those tumours where FGFR overexpression is indicative of a dependence on FGFR signalling. In this review, we provide a comprehensive and mechanistic overview of FGFR pathway aberrations and their functional consequences in paediatric cancer. We explore how FGFR over expression might be associated with true receptor activation. Further, we discuss the therapeutic implications of these aberrations in the paediatric setting and outline current and emerging therapeutic strategies to treat paediatric patients with FGFR-driven cancers. [Image: see text] Nature Publishing Group UK 2023-05-02 2023 /pmc/articles/PMC10244177/ /pubmed/37130917 http://dx.doi.org/10.1038/s41388-023-02705-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Article Brown, Lauren M. Ekert, Paul G. Fleuren, Emmy D. G. Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers |
title | Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers |
title_full | Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers |
title_fullStr | Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers |
title_full_unstemmed | Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers |
title_short | Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers |
title_sort | biological and clinical implications of fgfr aberrations in paediatric and young adult cancers |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244177/ https://www.ncbi.nlm.nih.gov/pubmed/37130917 http://dx.doi.org/10.1038/s41388-023-02705-7 |
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