FGFR-TKI resistance in cancer: current status and perspectives

Fibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concer...

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Autores principales: Yue, Sitong, Li, Yukun, Chen, Xiaojuan, Wang, Juan, Li, Meixiang, Chen, Yongheng, Wu, Daichao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Review
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876795/
https://www.ncbi.nlm.nih.gov/pubmed/33568192
http://dx.doi.org/10.1186/s13045-021-01040-2
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author Yue, Sitong
Li, Yukun
Chen, Xiaojuan
Wang, Juan
Li, Meixiang
Chen, Yongheng
Wu, Daichao
author_facet Yue, Sitong
Li, Yukun
Chen, Xiaojuan
Wang, Juan
Li, Meixiang
Chen, Yongheng
Wu, Daichao
author_sort Yue, Sitong
collection PubMed
description Fibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concern. Here, we review the mechanisms of FGFR-TKI resistance in cancer, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. In addition, we summarize strategies to overcome resistance, including developing covalent inhibitors, developing dual-target inhibitors, adopting combination therapy, and targeting lysosomes, which will facilitate the transition to precision medicine and individualized treatment.
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spelling pubmed-78767952021-02-11 FGFR-TKI resistance in cancer: current status and perspectives Yue, Sitong Li, Yukun Chen, Xiaojuan Wang, Juan Li, Meixiang Chen, Yongheng Wu, Daichao J Hematol Oncol Review Fibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concern. Here, we review the mechanisms of FGFR-TKI resistance in cancer, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. In addition, we summarize strategies to overcome resistance, including developing covalent inhibitors, developing dual-target inhibitors, adopting combination therapy, and targeting lysosomes, which will facilitate the transition to precision medicine and individualized treatment. BioMed Central 2021-02-10 /pmc/articles/PMC7876795/ /pubmed/33568192 http://dx.doi.org/10.1186/s13045-021-01040-2 Text en © The Author(s) 2021 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Yue, Sitong
Li, Yukun
Chen, Xiaojuan
Wang, Juan
Li, Meixiang
Chen, Yongheng
Wu, Daichao
FGFR-TKI resistance in cancer: current status and perspectives
title FGFR-TKI resistance in cancer: current status and perspectives
title_full FGFR-TKI resistance in cancer: current status and perspectives
title_fullStr FGFR-TKI resistance in cancer: current status and perspectives
title_full_unstemmed FGFR-TKI resistance in cancer: current status and perspectives
title_short FGFR-TKI resistance in cancer: current status and perspectives
title_sort fgfr-tki resistance in cancer: current status and perspectives
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876795/
https://www.ncbi.nlm.nih.gov/pubmed/33568192
http://dx.doi.org/10.1186/s13045-021-01040-2
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