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

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...

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Autores principales:	Jakub Szymczyk, Katarzyna Dominika Sluzalska, Izabela Materla, Lukasz Opalinski, Jacek Otlewski, Malgorzata Zakrzewska
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	FGF FGFR drug resistance cancer cancer treatment anti-cancer drugs Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e265c83e558d4be7976e7d68c9528fa3
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spelling	oai:doaj.org-article:e265c83e558d4be7976e7d68c9528fa32021-11-25T17:04:06ZFGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance10.3390/cancers132257962072-6694https://doaj.org/article/e265c83e558d4be7976e7d68c9528fa32021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5796https://doaj.org/toc/2072-6694Increased 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.Jakub SzymczykKatarzyna Dominika SluzalskaIzabela MaterlaLukasz OpalinskiJacek OtlewskiMalgorzata ZakrzewskaMDPI AGarticleFGFFGFRdrug resistancecancercancer treatmentanti-cancer drugsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5796, p 5796 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FGF FGFR drug resistance cancer cancer treatment anti-cancer drugs Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	FGF FGFR drug resistance cancer cancer treatment anti-cancer drugs Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jakub Szymczyk Katarzyna Dominika Sluzalska Izabela Materla Lukasz Opalinski Jacek Otlewski Malgorzata Zakrzewska FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
description	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.
format	article
author	Jakub Szymczyk Katarzyna Dominika Sluzalska Izabela Materla Lukasz Opalinski Jacek Otlewski Malgorzata Zakrzewska
author_facet	Jakub Szymczyk Katarzyna Dominika Sluzalska Izabela Materla Lukasz Opalinski Jacek Otlewski Malgorzata Zakrzewska
author_sort	Jakub Szymczyk
title	FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
title_short	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_sort	fgf/fgfr-dependent molecular mechanisms underlying anti-cancer drug resistance
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e265c83e558d4be7976e7d68c9528fa3
work_keys_str_mv	AT jakubszymczyk fgffgfrdependentmolecularmechanismsunderlyinganticancerdrugresistance AT katarzynadominikasluzalska fgffgfrdependentmolecularmechanismsunderlyinganticancerdrugresistance AT izabelamaterla fgffgfrdependentmolecularmechanismsunderlyinganticancerdrugresistance AT lukaszopalinski fgffgfrdependentmolecularmechanismsunderlyinganticancerdrugresistance AT jacekotlewski fgffgfrdependentmolecularmechanismsunderlyinganticancerdrugresistance AT malgorzatazakrzewska fgffgfrdependentmolecularmechanismsunderlyinganticancerdrugresistance
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FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance

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