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FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance

SIMPLE SUMMARY: Deregulation of the FGF/FGFR axis is associated with many types of cancer and contributes to the development of chemoresistance, limiting the effectiveness of current treatment strategies. There are several mechanisms involved in this phenomenon, including cross-talks with other sign...

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Autores principales: Szymczyk, Jakub, Sluzalska, Katarzyna Dominika, Materla, Izabela, Opalinski, Lukasz, Otlewski, Jacek, Zakrzewska, Malgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616288/
https://www.ncbi.nlm.nih.gov/pubmed/34830951
http://dx.doi.org/10.3390/cancers13225796
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author Szymczyk, Jakub
Sluzalska, Katarzyna Dominika
Materla, Izabela
Opalinski, Lukasz
Otlewski, Jacek
Zakrzewska, Malgorzata
author_facet Szymczyk, Jakub
Sluzalska, Katarzyna Dominika
Materla, Izabela
Opalinski, Lukasz
Otlewski, Jacek
Zakrzewska, Malgorzata
author_sort Szymczyk, Jakub
collection PubMed
description SIMPLE SUMMARY: Deregulation of the FGF/FGFR axis is associated with many types of cancer and contributes to the development of chemoresistance, limiting the effectiveness of current treatment strategies. There are several mechanisms involved in this phenomenon, including cross-talks with other signaling pathways, avoidance of apoptosis, stimulation of angiogenesis, and initiation of EMT. Here, we provide an overview of current research and approaches focusing on targeting components of the FGFR/FGF signaling module to overcome drug resistance during anti-cancer therapy. ABSTRACT: Increased expression of both FGF proteins and their receptors observed in many cancers is often associated with the development of chemoresistance, limiting the effectiveness of currently used anti-cancer therapies. Malfunctioning of the FGF/FGFR axis in cancer cells generates a number of molecular mechanisms that may affect the sensitivity of tumors to the applied drugs. Of key importance is the deregulation of cell signaling, which can lead to increased cell proliferation, survival, and motility, and ultimately to malignancy. Signaling pathways activated by FGFRs inhibit apoptosis, reducing the cytotoxic effect of some anti-cancer drugs. FGFRs-dependent signaling may also initiate angiogenesis and EMT, which facilitates metastasis and also correlates with drug resistance. Therefore, treatment strategies based on FGF/FGFR inhibition (using receptor inhibitors, ligand traps, monoclonal antibodies, or microRNAs) appear to be extremely promising. However, this approach may lead to further development of resistance through acquisition of specific mutations, metabolism switching, and molecular cross-talks. This review brings together information on the mechanisms underlying the involvement of the FGF/FGFR axis in the generation of drug resistance in cancer and highlights the need for further research to overcome this serious problem with novel therapeutic strategies.
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spelling pubmed-86162882021-11-26 FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance Szymczyk, Jakub Sluzalska, Katarzyna Dominika Materla, Izabela Opalinski, Lukasz Otlewski, Jacek Zakrzewska, Malgorzata Cancers (Basel) Review SIMPLE SUMMARY: Deregulation of the FGF/FGFR axis is associated with many types of cancer and contributes to the development of chemoresistance, limiting the effectiveness of current treatment strategies. There are several mechanisms involved in this phenomenon, including cross-talks with other signaling pathways, avoidance of apoptosis, stimulation of angiogenesis, and initiation of EMT. Here, we provide an overview of current research and approaches focusing on targeting components of the FGFR/FGF signaling module to overcome drug resistance during anti-cancer therapy. ABSTRACT: Increased expression of both FGF proteins and their receptors observed in many cancers is often associated with the development of chemoresistance, limiting the effectiveness of currently used anti-cancer therapies. Malfunctioning of the FGF/FGFR axis in cancer cells generates a number of molecular mechanisms that may affect the sensitivity of tumors to the applied drugs. Of key importance is the deregulation of cell signaling, which can lead to increased cell proliferation, survival, and motility, and ultimately to malignancy. Signaling pathways activated by FGFRs inhibit apoptosis, reducing the cytotoxic effect of some anti-cancer drugs. FGFRs-dependent signaling may also initiate angiogenesis and EMT, which facilitates metastasis and also correlates with drug resistance. Therefore, treatment strategies based on FGF/FGFR inhibition (using receptor inhibitors, ligand traps, monoclonal antibodies, or microRNAs) appear to be extremely promising. However, this approach may lead to further development of resistance through acquisition of specific mutations, metabolism switching, and molecular cross-talks. This review brings together information on the mechanisms underlying the involvement of the FGF/FGFR axis in the generation of drug resistance in cancer and highlights the need for further research to overcome this serious problem with novel therapeutic strategies. MDPI 2021-11-18 /pmc/articles/PMC8616288/ /pubmed/34830951 http://dx.doi.org/10.3390/cancers13225796 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Szymczyk, Jakub
Sluzalska, Katarzyna Dominika
Materla, Izabela
Opalinski, Lukasz
Otlewski, Jacek
Zakrzewska, Malgorzata
FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
title FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
title_full FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
title_fullStr FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
title_full_unstemmed FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
title_short FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
title_sort fgf/fgfr-dependent molecular mechanisms underlying anti-cancer drug resistance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616288/
https://www.ncbi.nlm.nih.gov/pubmed/34830951
http://dx.doi.org/10.3390/cancers13225796
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