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

• Type: Another Publication in an International Scientific Journal
• Date: 2022

Authors

Almeida, J (Author) Other; Mota, I (Author) Other; Skoda, J (Author) Other; Emilia Sousa (Author) FFUP; Honorina Cidade (Author) FFUP; Lucilia Saraiva (Author) FFUP

Journal

Title: Cancers

Vol. 14

Final page: 6212

ISSN: 2072-6694

Publisher: MDPI

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 1 Citation

Other information

Authenticus ID: P-00X-PHW

DOI: 10.3390/cancers14246212

Abstract (EN): 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. 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, Delta Np73, 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 23