Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Mutant p53 in Cancer Progression and Personalized Therapeutic Treatments

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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

Deadline for manuscript submissions: closed (10 October 2022) | Viewed by 12030

Share This Special Issue

Special Issue Editor

Prof. Dr. Sung Gwe Ahn

E-Mail Website
Guest Editor

Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea
Interests: breast cancer; triple-negative; mutant p53; TP53 mutation; molecular subtype

Special Issue Information

Dear Colleagues,

The TP53 tumor suppressor gene are frequently mutated in malignant tumors. As a tumor suppress gene, p53 can induce cell cycle arrest, apoptosis, senescence, or ferroptosis in response to stress signals and prevent the accumulation of cancer-causing mutations that lead to malignant tumors. Thus, loss of function of tumor suppressor p53 affect fundamental cellular pathways with cancer-promoting outcomes. Moreover, robust evidence suggests that gain-of-function of mutant p53 largely contributes to cancer progression. In an era of precision medicine, novel approaches targeting TP53 mutation with small molecules that can reactivate mutant p53 protein have been underway. We will include articles providing an overview of mutant p53 in cancer progression, with a focus on emerging evidence displaying mutant p53 targeted therapy as an addition to the personalized therapy arsenal.

Prof. Dr. Sung Gwe Ahn
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

mutant p53
TP53 mutation
tumorigenesis
gain-of-function
precision medicine
metastasis
therapeutic target
biomarkers
targeted therapy
breast cancer

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

20 pages, 4955 KiB

Open AccessArticle

Cytoplasmic p53β Isoforms Are Associated with Worse Disease-Free Survival in Breast Cancer

by Luiza Steffens Reinhardt, Kira Groen, Brianna C. Morten, Jean-Christophe Bourdon and Kelly A. Avery-Kiejda

Int. J. Mol. Sci. 2022, 23(12), 6670; https://doi.org/10.3390/ijms23126670 - 15 Jun 2022

Cited by 7 | Viewed by 2000

Abstract

TP53 mutations are associated with tumour progression, resistance to therapy and poor prognosis. However, in breast cancer, TP53′s overall mutation frequency is lower than expected (~25%), suggesting that other mechanisms may be responsible for the disruption of this critical tumour suppressor. p53 isoforms are known to enhance or disrupt p53 pathway activity in cell- and context-specific manners. Our previous study revealed that p53 isoform mRNA expression correlates with clinicopathological features and survival in breast cancer and may account for the dysregulation of the p53 pathway in the absence of TP53 mutations. Hence, in this study, the protein expression of p53 isoforms, transactivation domain p53 (TAp53), p53β, Δ40p53, Δ133p53 and Δ160p53 was analysed using immunohistochemistry in a cohort of invasive ductal carcinomas (n = 108). p53 isoforms presented distinct cellular localisation, with some isoforms being expressed in tumour cells and others in infiltrating immune cells. Moreover, high levels of p53β, most likely to be N-terminally truncated β variants, were significantly associated with worse disease-free survival, especially in tumours with wild-type TP53. To the best of our knowledge, this is the first study that analysed the endogenous protein levels of p53 isoforms in a breast cancer cohort. Our findings suggest that p53β may be a useful prognostic marker. Full article

(This article belongs to the Special Issue Mutant p53 in Cancer Progression and Personalized Therapeutic Treatments)

► Show Figures

Graphical abstract

14 pages, 2063 KiB

Open AccessArticle

VPA and TSA Interrupt the Interplay between mutp53 and HSP70, Leading to CHK1 and RAD51 Down-Regulation and Sensitizing Pancreatic Cancer Cells to AZD2461 PARP Inhibitor

by Maria Anele Romeo, Maria Saveria Gilardini Montani, Rossella Benedetti, Andrea Arena, Gabriella D’Orazi and Mara Cirone

Int. J. Mol. Sci. 2022, 23(4), 2268; https://doi.org/10.3390/ijms23042268 - 18 Feb 2022

Cited by 12 | Viewed by 2275

Abstract

HDAC inhibitors (HDACi) represent promising anti-cancer treatments, as the acetylation of histone and non-histone proteins is often dysregulated in cancer and contributes to cancer onset and progression. HDACi have been also reported to increase the cytotoxicity of DNA-damaging agents, such as radiation or cisplatin. In this study, we found that TSA and, even more effectively, VPA synergized with AZD2461, PARP1, 2 and 3 inhibitor (PARPi) to induce DNA damage and reduce pancreatic cancer cell survival. At a molecular level, VPA and TSA down-regulated CHK1 and RAD51, which is correlated with the interruption of the cross-talk between mutp53 and HSP70. Moreover, VPA and to a lesser extent TSA reactivated wtp53 in these cells, which contributed to CHK1 and RAD51 reduction. These findings suggest that the combination of HDACi and PARPi might improve the treatment of pancreatic cancer, which remains one of the most aggressive and therapy-resistant cancers. Full article

(This article belongs to the Special Issue Mutant p53 in Cancer Progression and Personalized Therapeutic Treatments)

► Show Figures

Graphical abstract

Review

Jump to: Research

13 pages, 1390 KiB

Open AccessReview

NRF2 in Cancer: Cross-Talk with Oncogenic Pathways and Involvement in Gammaherpesvirus-Driven Carcinogenesis

by Mara Cirone and Gabriella D’Orazi

Int. J. Mol. Sci. 2023, 24(1), 595; https://doi.org/10.3390/ijms24010595 - 29 Dec 2022

Cited by 9 | Viewed by 2532

Abstract

Expanding knowledge of the molecular mechanisms at the basis of tumor development, especially the cross-talk between oncogenic pathways, will possibly lead to better tailoring of anticancer therapies. Nuclear factor erythroid 2-related factor 2 (NRF2) plays a central role in cancer progression, not only because of its antioxidant activity but also because it establishes cross-talk with several oncogenic pathways, including Heat Shock Factor1 (HSF1), mammalian target of rapamycin (mTOR), and mutant (mut) p53. Moreover, the involvement of NRF2 in gammaherpesvirus-driven carcinogenesis is particularly interesting. These viruses indeed hijack the NRF2 pathway to sustain the survival of tumor cells in which they establish a latent infection and to avoid a too-high increase of reactive oxygen species (ROS) when these cancer cells undergo treatments that induce viral replication. Interestingly, NRF2 activation may prevent gammaherpesvirus-driven oncogenic transformation, highlighting how manipulating the NRF2 pathway in the different phases of gammaherpesvirus-mediated carcinogenesis may lead to different outcomes. This review will highlight the mechanistic interplay between NRF2 and some oncogenic pathways and its involvement in gammaherpesviruses biology to recapitulate published evidence useful for potential application in cancer therapy. Full article

(This article belongs to the Special Issue Mutant p53 in Cancer Progression and Personalized Therapeutic Treatments)

► Show Figures

Figure 1

15 pages, 619 KiB

Open AccessReview

Gain of Function (GOF) Mutant p53 in Cancer—Current Therapeutic Approaches

by Katarzyna A. Roszkowska, Aleksandra Piecuch, Maria Sady, Zdzisław Gajewski and Sylwia Flis

Int. J. Mol. Sci. 2022, 23(21), 13287; https://doi.org/10.3390/ijms232113287 - 31 Oct 2022

Cited by 12 | Viewed by 2224

Abstract

Continuous development of personalized treatments is undoubtedly beneficial for oncogenic patients’ comfort and survival rate. Mutant TP53 is associated with a worse prognosis due to the occurrence of metastases, increased chemoresistance, and tumor growth. Currently, numerous compounds capable of p53 reactivation or the destabilization of mutant p53 are being investigated. Several of them, APR-246, COTI-2, SAHA, and PEITC, were approved for clinical trials. This review focuses on these novel therapeutic opportunities, their mechanisms of action, and their significance for potential medical application. Full article

(This article belongs to the Special Issue Mutant p53 in Cancer Progression and Personalized Therapeutic Treatments)

► Show Figures

Figure 1

19 pages, 2965 KiB

Open AccessReview

Anticancer Therapeutic Strategies Targeting p53 Aggregation

by Giulia D. S. Ferretti, Julia Quarti, Gileno dos Santos, Luciana P. Rangel and Jerson L. Silva

Int. J. Mol. Sci. 2022, 23(19), 11023; https://doi.org/10.3390/ijms231911023 - 20 Sep 2022

Cited by 5 | Viewed by 2076

Abstract

p53 is a tumor suppressor protein that is mutated in more than 50% of cancer cases. When mutated, it frequently results in p53 oncogenic gain of function (GOF), resulting in a greater tendency to aggregate in the phase separation and phase transition pathway. GOFs related to p53 aggregation include chemoresistance, which makes therapy even more difficult. The therapies available for the treatment of cancer are still quite limited, so the study of new molecules and therapeutic targets focusing on p53 aggregates is a promising strategy against cancer. In this review, we classify anticancer molecules with antiaggregation properties into four categories: thiol alkylating agents, designed peptides, agents with chaperone-based mechanisms that inhibit p53 aggregation, and miscellaneous compounds with anti-protein aggregation properties that have been studied in neurodegenerative diseases. Furthermore, we highlight autophagy as a possible degradation pathway for aggregated p53. Here, considering cancer as a protein aggregation disease, we review strategies that have been used to disrupt p53 aggregates, leading to cancer regression. Full article

(This article belongs to the Special Issue Mutant p53 in Cancer Progression and Personalized Therapeutic Treatments)

► Show Figures