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Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment

SIMPLE SUMMARY: Neuroblastoma is the most common extracranial pediatric tumor. Although children with low- and intermediate-risk neuroblastoma, which correspond to approximately half of all newly diagnosed cases, have a good event-free and overall survival, high-risk neuroblastoma can be extremely a...

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Autores principales: Almeida, Joana, Mota, Inês, Skoda, Jan, Sousa, Emília, Cidade, Honorina, Saraiva, Lucília
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777536/
https://www.ncbi.nlm.nih.gov/pubmed/36551697
http://dx.doi.org/10.3390/cancers14246212
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author Almeida, Joana
Mota, Inês
Skoda, Jan
Sousa, Emília
Cidade, Honorina
Saraiva, Lucília
author_facet Almeida, Joana
Mota, Inês
Skoda, Jan
Sousa, Emília
Cidade, Honorina
Saraiva, Lucília
author_sort Almeida, Joana
collection PubMed
description SIMPLE SUMMARY: Neuroblastoma is the most common extracranial pediatric tumor. Although children with low- and intermediate-risk neuroblastoma, which correspond to approximately half of all newly diagnosed cases, have a good event-free and overall survival, high-risk neuroblastoma can be extremely aggressive and hard-to-treat tumors. In neuroblastoma, p53 and TAp73 act as safeguards against malignant transformation, but they are commonly inhibited by negative regulators, such as MDMs, Itch, and Aurora kinase A. This review focuses on the relevant tumor suppressor role of p53 and TAp73 in neuroblastoma, further addressing their connection with crucial biomarkers of poor prognosis, such as N-MYC, and their great potential as therapeutic targets. ABSTRACT: Neuroblastoma (NB) is an embryonic cancer that develops from neural crest stem cells, being one of the most common malignancies in children. The clinical manifestation of this disease is highly variable, ranging from spontaneous regression to increased aggressiveness, which makes it a major therapeutic challenge in pediatric oncology. The p53 family proteins p53 and TAp73 play a key role in protecting cells against genomic instability and malignant transformation. However, in NB, their activities are commonly inhibited by interacting proteins such as murine double minute (MDM)2 and MDMX, mutant p53, ΔNp73, Itch, and Aurora kinase A. The interplay between the p53/TAp73 pathway and N-MYC, a known biomarker of poor prognosis and drug resistance in NB, also proves to be decisive in the pathogenesis of this tumor. More recently, a strong crosstalk between microRNAs (miRNAs) and p53/TAp73 has been established, which has been the focused of great attention because of its potential for developing new therapeutic strategies. Collectively, this review provides an updated overview about the critical role of the p53/TAp73 pathway in the pathogenesis of NB, highlighting encouraging clues for the advance of alternative NB targeted therapies.
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spelling pubmed-97775362022-12-23 Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment Almeida, Joana Mota, Inês Skoda, Jan Sousa, Emília Cidade, Honorina Saraiva, Lucília Cancers (Basel) Review SIMPLE SUMMARY: Neuroblastoma is the most common extracranial pediatric tumor. Although children with low- and intermediate-risk neuroblastoma, which correspond to approximately half of all newly diagnosed cases, have a good event-free and overall survival, high-risk neuroblastoma can be extremely aggressive and hard-to-treat tumors. In neuroblastoma, p53 and TAp73 act as safeguards against malignant transformation, but they are commonly inhibited by negative regulators, such as MDMs, Itch, and Aurora kinase A. This review focuses on the relevant tumor suppressor role of p53 and TAp73 in neuroblastoma, further addressing their connection with crucial biomarkers of poor prognosis, such as N-MYC, and their great potential as therapeutic targets. ABSTRACT: Neuroblastoma (NB) is an embryonic cancer that develops from neural crest stem cells, being one of the most common malignancies in children. The clinical manifestation of this disease is highly variable, ranging from spontaneous regression to increased aggressiveness, which makes it a major therapeutic challenge in pediatric oncology. The p53 family proteins p53 and TAp73 play a key role in protecting cells against genomic instability and malignant transformation. However, in NB, their activities are commonly inhibited by interacting proteins such as murine double minute (MDM)2 and MDMX, mutant p53, ΔNp73, Itch, and Aurora kinase A. The interplay between the p53/TAp73 pathway and N-MYC, a known biomarker of poor prognosis and drug resistance in NB, also proves to be decisive in the pathogenesis of this tumor. More recently, a strong crosstalk between microRNAs (miRNAs) and p53/TAp73 has been established, which has been the focused of great attention because of its potential for developing new therapeutic strategies. Collectively, this review provides an updated overview about the critical role of the p53/TAp73 pathway in the pathogenesis of NB, highlighting encouraging clues for the advance of alternative NB targeted therapies. MDPI 2022-12-16 /pmc/articles/PMC9777536/ /pubmed/36551697 http://dx.doi.org/10.3390/cancers14246212 Text en © 2022 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
Almeida, Joana
Mota, Inês
Skoda, Jan
Sousa, Emília
Cidade, Honorina
Saraiva, Lucília
Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment
title Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment
title_full Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment
title_fullStr Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment
title_full_unstemmed Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment
title_short Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment
title_sort deciphering the role of p53 and tap73 in neuroblastoma: from pathogenesis to treatment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777536/
https://www.ncbi.nlm.nih.gov/pubmed/36551697
http://dx.doi.org/10.3390/cancers14246212
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