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p53 as a biomarker and potential target in gastrointestinal stromal tumors

KIT and PDGFRA play a major role in the oncogenic process in gastrointestinal stroma tumors (GIST) and small molecules have been employed with great success to target the KIT and PDGFRA pathways in this cancer. However, approximately 10% of patients with GIST are resistant to current targeted drug t...

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Autores principales: Wu, Chiao-En, Chen, Chiao-Ping, Huang, Wen-Kuan, Pan, Yi-Ru, Aptullahoglu, Erhan, Yeh, Chun-Nan, Lunec, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372431/
https://www.ncbi.nlm.nih.gov/pubmed/35965531
http://dx.doi.org/10.3389/fonc.2022.872202
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author Wu, Chiao-En
Chen, Chiao-Ping
Huang, Wen-Kuan
Pan, Yi-Ru
Aptullahoglu, Erhan
Yeh, Chun-Nan
Lunec, John
author_facet Wu, Chiao-En
Chen, Chiao-Ping
Huang, Wen-Kuan
Pan, Yi-Ru
Aptullahoglu, Erhan
Yeh, Chun-Nan
Lunec, John
author_sort Wu, Chiao-En
collection PubMed
description KIT and PDGFRA play a major role in the oncogenic process in gastrointestinal stroma tumors (GIST) and small molecules have been employed with great success to target the KIT and PDGFRA pathways in this cancer. However, approximately 10% of patients with GIST are resistant to current targeted drug therapy. There is a need to explore other potential targets. Although p53 alterations frequently occur in most cancers, studies regarding p53 in GIST have been limited. The CDKN2A/MDM2/p53 axis regulates cell cycle progression and DNA damage responses, which in turn control tumor growth. This axis is the major event required for transformation from low- to high-risk GIST. Generally, p53 mutation is infrequent in GIST, but p53 overexpression has been reported to be associated with high-risk GIST and unfavorable prognosis, implying that p53 should play a critical role in GIST. Also, Wee1 regulates the cell cycle and the antitumor activity of Wee1 inhibition was reported to be p53 mutant dependent. In addition, Wee1 was reported to have potential activity in GIST through the regulation of KIT protein and this mechanism may be dependent on p53 status. In this article, we review previous reports regarding the role of p53 in GIST and propose targeting the p53 pathway as a novel additional treatment strategy for GIST.
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spelling pubmed-93724312022-08-13 p53 as a biomarker and potential target in gastrointestinal stromal tumors Wu, Chiao-En Chen, Chiao-Ping Huang, Wen-Kuan Pan, Yi-Ru Aptullahoglu, Erhan Yeh, Chun-Nan Lunec, John Front Oncol Oncology KIT and PDGFRA play a major role in the oncogenic process in gastrointestinal stroma tumors (GIST) and small molecules have been employed with great success to target the KIT and PDGFRA pathways in this cancer. However, approximately 10% of patients with GIST are resistant to current targeted drug therapy. There is a need to explore other potential targets. Although p53 alterations frequently occur in most cancers, studies regarding p53 in GIST have been limited. The CDKN2A/MDM2/p53 axis regulates cell cycle progression and DNA damage responses, which in turn control tumor growth. This axis is the major event required for transformation from low- to high-risk GIST. Generally, p53 mutation is infrequent in GIST, but p53 overexpression has been reported to be associated with high-risk GIST and unfavorable prognosis, implying that p53 should play a critical role in GIST. Also, Wee1 regulates the cell cycle and the antitumor activity of Wee1 inhibition was reported to be p53 mutant dependent. In addition, Wee1 was reported to have potential activity in GIST through the regulation of KIT protein and this mechanism may be dependent on p53 status. In this article, we review previous reports regarding the role of p53 in GIST and propose targeting the p53 pathway as a novel additional treatment strategy for GIST. Frontiers Media S.A. 2022-07-29 /pmc/articles/PMC9372431/ /pubmed/35965531 http://dx.doi.org/10.3389/fonc.2022.872202 Text en Copyright © 2022 Wu, Chen, Huang, Pan, Aptullahoglu, Yeh and Lunec 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 Oncology
Wu, Chiao-En
Chen, Chiao-Ping
Huang, Wen-Kuan
Pan, Yi-Ru
Aptullahoglu, Erhan
Yeh, Chun-Nan
Lunec, John
p53 as a biomarker and potential target in gastrointestinal stromal tumors
title p53 as a biomarker and potential target in gastrointestinal stromal tumors
title_full p53 as a biomarker and potential target in gastrointestinal stromal tumors
title_fullStr p53 as a biomarker and potential target in gastrointestinal stromal tumors
title_full_unstemmed p53 as a biomarker and potential target in gastrointestinal stromal tumors
title_short p53 as a biomarker and potential target in gastrointestinal stromal tumors
title_sort p53 as a biomarker and potential target in gastrointestinal stromal tumors
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372431/
https://www.ncbi.nlm.nih.gov/pubmed/35965531
http://dx.doi.org/10.3389/fonc.2022.872202
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