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P53: Mechanisms in DNA Damage Repair Responses and Roles in Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 12965

Special Issue Editor


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Guest Editor
School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, NSW 2305, Australia
Interests: p53; DNA damage response; precision oncology; therapy resistance; tumor heterogeneity

Special Issue Information

Dear Colleagues,

Since its discovery forty-five years ago, p53 has solidified its status as a vital tumour suppressor, crucial for maintaining genome stability. Despite extensive research, understanding the intricate role of p53 in tumour initiation and progression remains a challenge.

This IJMS Special Issue aims to address critical questions raised in contemporary literature, such as the confusion surrounding p53 research, the perceived limitations of precision oncology involving p53-based therapies and the importance of DNA repair pathways in therapeutic contexts. Moreover, it aims to scrutinise the definition of cell death and its implications in cancer biology.

The purpose of this Special Issue is to shed light on the multifaceted roles of p53 in DNA damage responses. Authors are encouraged to explore the challenges associated with implementing p53-based therapies, including tumour heterogeneity and therapy resistance, as well as dormancy mechanisms, such as polyploid/multinucleated giant cells (PGCCs) and reversible senescence in the context of p53-mediated responses. Furthermore, this Special Issue aims to delve into apoptosis-related phenomena, including anastasis, Phoenix Rising and Treacherous Apoptosis, highlighting their impact on cancer progression. Original studies elucidating novel aspects of the p53 family protein and isoform function and investigations into the epigenetic mechanisms governing p53 regulation are also of interest.

In summary, this Special Issue seeks to update our understanding of complex roles of p53 in DNA damage responses and cancer pathogenesis. By addressing the current challenges and exploring novel avenues of research, it aims to pave the way for improved strategies in p53-based cancer therapy.

Dr. Luiza Steffens Reinhardt
Guest Editor

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Keywords

  • p53
  • DNA damage response
  • precision oncology
  • therapy resistance
  • tumor heterogeneity
  • apoptosis
  • anastasis
  • PGCCs
  • Phoenix Rising
  • Treacherous Apoptosis

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Published Papers (2 papers)

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Research

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19 pages, 2610 KB  
Article
Rationale for Testing TP53 Mutations in Thyroid Cancer—Original Data and Meta-Analysis
by Katarzyna Lacka, Adam Maciejewski, Piotr Tyburski, Ewa Manuszewska-Jopek, Przemysław Majewski and Barbara Więckowska
Int. J. Mol. Sci. 2025, 26(3), 1035; https://doi.org/10.3390/ijms26031035 - 25 Jan 2025
Cited by 5 | Viewed by 2607
Abstract
The p53 protein is a tumor-suppressing transcription factor that is critical in tumorigenesis. While TP53 mutations are rare in differentiated thyroid cancer (DTC), they are significantly more common in anaplastic thyroid cancer (ATC). This study presents original results and a meta-analysis reevaluating the [...] Read more.
The p53 protein is a tumor-suppressing transcription factor that is critical in tumorigenesis. While TP53 mutations are rare in differentiated thyroid cancer (DTC), they are significantly more common in anaplastic thyroid cancer (ATC). This study presents original results and a meta-analysis reevaluating the prognostic value of TP53 mutations in thyroid cancer, including surrogate markers such as immunohistochemical p53 expression and serum p53-Abs levels. TP53 mutations were analyzed using SSSP and direct sequencing in a DTC group (15 patients), an ATC group (3 patients), and a control group (25 patients). The immunohistochemical p53 expression was assessed in tissue samples. A meta-analysis of 14 eligible studies identified through the PubMed, Scopus, Google Scholar, and Cochrane databases was conducted. Our results showed TP53 mutations in all ATC cases, 6.67% of DTC cases (1 out of 15), and none in the control group. Immunohistochemical p53 overexpression was observed in 4 out of 15 DTC (26.67%) and all ATC cases but absent in controls. A meta-analysis confirmed that TP53 mutations are significantly more frequent in ATC than controls (OR 8.95; 95% CI: 1.36–58.70; p = 0.02) but not in DTC vs. controls (OR 1.87; 95% CI: 0.53–6.58; p = 0.33). p53 overexpression was significantly higher in both DTC and ATC vs. controls (OR 7.99; 95% CI: 5.11–12.51; p < 0.01 and OR 64.37; 95% CI: 27.28–151.89; p < 0.01, respectively). The serum p53-Abs positivity was also elevated in patients with PTC vs. controls (OR 2.07; 95% CI: 1.24–3.47; p < 0.01). TP53 mutations are frequent events in the pathogenesis of ATC. In DTC, further prospective studies are needed to determine the prognostic value of TP53 mutations and related surrogate markers (immunohistochemical p53 expression, p53-Abs positivity). Full article
(This article belongs to the Special Issue P53: Mechanisms in DNA Damage Repair Responses and Roles in Cancer)
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Review

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27 pages, 7120 KB  
Review
Unraveling the Guardian: p53’s Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies
by Han Zhang, Jianxiong Xu, Yuxuan Long, Ayitila Maimaitijiang, Zhengding Su, Wenfang Li and Jinyao Li
Int. J. Mol. Sci. 2024, 25(23), 12928; https://doi.org/10.3390/ijms252312928 - 1 Dec 2024
Cited by 30 | Viewed by 9555
Abstract
DNA damage can lead to mutations that can alter the function of oncogenes or tumor suppressor genes, thus promoting the development of cancer. p53 plays a multifaceted and complex role in the DNA damage response and cancer progression and is known as the [...] Read more.
DNA damage can lead to mutations that can alter the function of oncogenes or tumor suppressor genes, thus promoting the development of cancer. p53 plays a multifaceted and complex role in the DNA damage response and cancer progression and is known as the ‘guardian of the gene’. When DNA damage occurs, p53 is activated through a series of post-translational modifications, which stabilize the protein and enhance its function as a transcription factor. It regulates processes including cell cycle checkpoints, DNA repair and apoptosis, thereby preventing the spread of damaged DNA and maintaining genome integrity. On the one hand, p53 can initiate cell cycle arrest and induce cells to enter the G1/S and G2/M checkpoints, preventing cells with damaged DNA from continuing to proliferate and gaining time for DNA repair. At the same time, p53 can promote the activation of DNA repair pathways, including base excision repair, nucleotide excision repair and other repair pathways, to ensure the integrity of genetic material. If the damage is too severe to repair, p53 will trigger the apoptosis process to eliminate potential cancer risks in time. p53 also plays a pivotal role in cancer progression. Mutations in the p53 gene are frequently found in many cancers, and the mutated p53 not only loses its normal tumor suppressor function but may even acquire pro-cancer activity. Therefore, we also discuss therapeutic strategies targeting the p53 pathway, such as the use of small-molecule drugs to restore the function of wild-type p53, the inhibition of negative regulatory factors and synthetic lethality approaches for p53-deficient tumors. This review therefore highlights the important role of p53 in maintaining genomic stability and its potential in therapeutic strategies for cancer. Full article
(This article belongs to the Special Issue P53: Mechanisms in DNA Damage Repair Responses and Roles in Cancer)
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