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Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets

Hepatocellular carcinoma (HCC) is a type of primary liver cancer with poor prognosis, and its incidence and mortality rate are increasing worldwide. It is refractory to conventional chemotherapy and radiotherapy owing to its high tumor heterogeneity. Accumulated genetic alterations and aberrant cell...

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Autores principales: Wang, Haijun, Yang, Jie, Zhang, Ke, Liu, Jia, Li, Yushan, Su, Wei, Song, Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082422/
https://www.ncbi.nlm.nih.gov/pubmed/33935756
http://dx.doi.org/10.3389/fphar.2021.650388
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author Wang, Haijun
Yang, Jie
Zhang, Ke
Liu, Jia
Li, Yushan
Su, Wei
Song, Na
author_facet Wang, Haijun
Yang, Jie
Zhang, Ke
Liu, Jia
Li, Yushan
Su, Wei
Song, Na
author_sort Wang, Haijun
collection PubMed
description Hepatocellular carcinoma (HCC) is a type of primary liver cancer with poor prognosis, and its incidence and mortality rate are increasing worldwide. It is refractory to conventional chemotherapy and radiotherapy owing to its high tumor heterogeneity. Accumulated genetic alterations and aberrant cell signaling pathway have been characterized in HCC. The fibroblast growth factor (FGF) family and their receptors (FGFRs) are involved in diverse biological activities, including embryonic development, proliferation, differentiation, survival, angiogenesis, and migration, etc. Data mining results of The Cancer Genome Atlas demonstrate high levels of FGF and/or FGFR expression in HCC tumors compared with normal tissues. Moreover, substantial evidence indicates that the FGF/FGFR signaling axis plays an important role in various mechanisms that contribute to HCC development. At present, several inhibitors targeting FGF/FGFR, such as multikinase inhibitors, specific FGFR4 inhibitors, and FGF ligand traps, exhibit antitumor activity in preclinical or early development phases in HCC. In this review, we summarize the research progress regarding the molecular implications of FGF/FGFR-mediated signaling and the development of FGFR-targeted therapeutics in hepatocarcinogenesis.
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spelling pubmed-80824222021-04-30 Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets Wang, Haijun Yang, Jie Zhang, Ke Liu, Jia Li, Yushan Su, Wei Song, Na Front Pharmacol Pharmacology Hepatocellular carcinoma (HCC) is a type of primary liver cancer with poor prognosis, and its incidence and mortality rate are increasing worldwide. It is refractory to conventional chemotherapy and radiotherapy owing to its high tumor heterogeneity. Accumulated genetic alterations and aberrant cell signaling pathway have been characterized in HCC. The fibroblast growth factor (FGF) family and their receptors (FGFRs) are involved in diverse biological activities, including embryonic development, proliferation, differentiation, survival, angiogenesis, and migration, etc. Data mining results of The Cancer Genome Atlas demonstrate high levels of FGF and/or FGFR expression in HCC tumors compared with normal tissues. Moreover, substantial evidence indicates that the FGF/FGFR signaling axis plays an important role in various mechanisms that contribute to HCC development. At present, several inhibitors targeting FGF/FGFR, such as multikinase inhibitors, specific FGFR4 inhibitors, and FGF ligand traps, exhibit antitumor activity in preclinical or early development phases in HCC. In this review, we summarize the research progress regarding the molecular implications of FGF/FGFR-mediated signaling and the development of FGFR-targeted therapeutics in hepatocarcinogenesis. Frontiers Media S.A. 2021-04-15 /pmc/articles/PMC8082422/ /pubmed/33935756 http://dx.doi.org/10.3389/fphar.2021.650388 Text en Copyright © 2021 Wang, Yang, Zhang, Liu, Li, Su and Song. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Haijun
Yang, Jie
Zhang, Ke
Liu, Jia
Li, Yushan
Su, Wei
Song, Na
Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets
title Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets
title_full Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets
title_fullStr Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets
title_full_unstemmed Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets
title_short Advances of Fibroblast Growth Factor/Receptor Signaling Pathway in Hepatocellular Carcinoma and its Pharmacotherapeutic Targets
title_sort advances of fibroblast growth factor/receptor signaling pathway in hepatocellular carcinoma and its pharmacotherapeutic targets
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082422/
https://www.ncbi.nlm.nih.gov/pubmed/33935756
http://dx.doi.org/10.3389/fphar.2021.650388
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