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Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy
Oncogenic activation of the fibroblast growth factor receptor (FGFR) through mutations and fusions of the FGFR gene occur in a variety of different malignancies such as urothelial carcinoma and cholangiocarcinoma. Inhibition of the kinase domain of the FGFR with targeted oral FGFR inhibitors has bee...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
OAE Publishing Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992533/ https://www.ncbi.nlm.nih.gov/pubmed/35582593 http://dx.doi.org/10.20517/cdr.2019.42 |
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author | Lau, David K. Jenkins, Laura Weickhardt, Andrew |
author_facet | Lau, David K. Jenkins, Laura Weickhardt, Andrew |
author_sort | Lau, David K. |
collection | PubMed |
description | Oncogenic activation of the fibroblast growth factor receptor (FGFR) through mutations and fusions of the FGFR gene occur in a variety of different malignancies such as urothelial carcinoma and cholangiocarcinoma. Inhibition of the kinase domain of the FGFR with targeted oral FGFR inhibitors has been shown in both preclinical and early phase clinical trials to lead to meaningful reductions in tumour size and larger confirmatory randomized trials are underway. Acquired resistance to FGFR inhibition using a variety of mechanisms that includes, activation of alternate signaling pathways and expansion of tumour clones with gatekeeper mutations in the FGFR gene. This review summarizes the acquired resistance mechanisms to FGFR therapy and therapeutic approaches to circumventing resistance. |
format | Online Article Text |
id | pubmed-8992533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | OAE Publishing Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89925332022-05-16 Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy Lau, David K. Jenkins, Laura Weickhardt, Andrew Cancer Drug Resist Review Oncogenic activation of the fibroblast growth factor receptor (FGFR) through mutations and fusions of the FGFR gene occur in a variety of different malignancies such as urothelial carcinoma and cholangiocarcinoma. Inhibition of the kinase domain of the FGFR with targeted oral FGFR inhibitors has been shown in both preclinical and early phase clinical trials to lead to meaningful reductions in tumour size and larger confirmatory randomized trials are underway. Acquired resistance to FGFR inhibition using a variety of mechanisms that includes, activation of alternate signaling pathways and expansion of tumour clones with gatekeeper mutations in the FGFR gene. This review summarizes the acquired resistance mechanisms to FGFR therapy and therapeutic approaches to circumventing resistance. OAE Publishing Inc. 2019-09-19 /pmc/articles/PMC8992533/ /pubmed/35582593 http://dx.doi.org/10.20517/cdr.2019.42 Text en © The Author(s) 2019. https://creativecommons.org/licenses/by/4.0/© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, 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. |
spellingShingle | Review Lau, David K. Jenkins, Laura Weickhardt, Andrew Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy |
title | Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy |
title_full | Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy |
title_fullStr | Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy |
title_full_unstemmed | Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy |
title_short | Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy |
title_sort | mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992533/ https://www.ncbi.nlm.nih.gov/pubmed/35582593 http://dx.doi.org/10.20517/cdr.2019.42 |
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