Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2019

Open Access 01-12-2019 | Commentary

Targeting mutant p53 in cancer: the latest insights

Authors: Silvia Di Agostino, Giulia Fontemaggi, Sabrina Strano, Giovanni Blandino, Gabriella D’Orazi

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

Login to get access

Abstract

This commentary wishes to highlight the latest discoveries in the mutant p53 field that have been discussed in the 8th p53 Mutant Workshop 2019, held in Lyon. TP53 mutant (mutp53) proteins are involved in the pathogenesis of most human cancers. Mutp53 proteins not only lose wild-typ53 function but, in some circumstances, may acquire novel oncogenic functions, namely gain-of-function (GOF), which lead to aberrant cell proliferation, chemoresistance, disruption of tissue architecture, migration, invasion and metastasis. Decoding the TP53 mutational spectrum and mutp53 interaction with additional transcription factors will therefore help to developing and testing novel and hopefully more efficient combinatorial therapeutic approaches.
Literature
1.
go back to reference Mantovani F, Collavin LDS. G: mutant p53 as a guardian of the cancer cells. Cell Death Differ. 2019;26:199–212.CrossRef Mantovani F, Collavin LDS. G: mutant p53 as a guardian of the cancer cells. Cell Death Differ. 2019;26:199–212.CrossRef
2.
go back to reference D'Orazi G, Cirone M. Mutant p53 and cellular stress pathways: a criminal alliance that promotes cancer progression. Cancers (Basel). 2019;11:E614.CrossRef D'Orazi G, Cirone M. Mutant p53 and cellular stress pathways: a criminal alliance that promotes cancer progression. Cancers (Basel). 2019;11:E614.CrossRef
3.
go back to reference Guha T, Malkin D. Inherited TP53 mutations and the li-Fraumeni syndrome. Cold Spring Harb Perspect Med. 2017;3:7. Guha T, Malkin D. Inherited TP53 mutations and the li-Fraumeni syndrome. Cold Spring Harb Perspect Med. 2017;3:7.
4.
go back to reference Ballinger ML, Best A, Mail PL, Khincha PP, Loud JT, Peters JA, et al. Baseline surveillance in li-Fraumeni syndrome using whole-body magnetic resonance imaging: a meta-analysis. JAMA Oncol. 2017;3:1634–9.CrossRef Ballinger ML, Best A, Mail PL, Khincha PP, Loud JT, Peters JA, et al. Baseline surveillance in li-Fraumeni syndrome using whole-body magnetic resonance imaging: a meta-analysis. JAMA Oncol. 2017;3:1634–9.CrossRef
5.
go back to reference Greathouse KL, White JR, Vargas AJ, Bliskovsky VV, Beck JA, von Muhlinen N, et al. Interaction between the microbiome and TP53 in human lung cancer. Genome Biol. 2018;19:123.CrossRef Greathouse KL, White JR, Vargas AJ, Bliskovsky VV, Beck JA, von Muhlinen N, et al. Interaction between the microbiome and TP53 in human lung cancer. Genome Biol. 2018;19:123.CrossRef
6.
go back to reference Cooks T, Pateras IS, Jenkins LM, Patel KM, Robles AI, Morris J, et al. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat Commun. 2018;9:771.CrossRef Cooks T, Pateras IS, Jenkins LM, Patel KM, Robles AI, Morris J, et al. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat Commun. 2018;9:771.CrossRef
7.
go back to reference Frixa T, Donzelli S, Blandino G. Oncogenic MicroRNAs: key players in malignant transformation. Cancers (Basel). 2015;7(4):2466–85.CrossRef Frixa T, Donzelli S, Blandino G. Oncogenic MicroRNAs: key players in malignant transformation. Cancers (Basel). 2015;7(4):2466–85.CrossRef
8.
go back to reference Lozano G. The oncogenic roles of p53 mutants in mouse models. Curr Opin Genet Dev. 2007;17:66–70.CrossRef Lozano G. The oncogenic roles of p53 mutants in mouse models. Curr Opin Genet Dev. 2007;17:66–70.CrossRef
9.
go back to reference Blandino G, Di Agostino S. New therapeutic strategies to treat cancers expressing mutant p53 proteins. J Exp Clin Cancer Res. 2018;37:30.CrossRef Blandino G, Di Agostino S. New therapeutic strategies to treat cancers expressing mutant p53 proteins. J Exp Clin Cancer Res. 2018;37:30.CrossRef
10.
go back to reference Miranda PJ, Buckley D, Raghu D, Pang JB, Takano EA, Vijayakumaran R, et al. MDM4 is a rational target for treating breast cancers with mutant p53. J Pathol. 2017;241:661–70.CrossRef Miranda PJ, Buckley D, Raghu D, Pang JB, Takano EA, Vijayakumaran R, et al. MDM4 is a rational target for treating breast cancers with mutant p53. J Pathol. 2017;241:661–70.CrossRef
Metadata
Title
Targeting mutant p53 in cancer: the latest insights
Authors
Silvia Di Agostino
Giulia Fontemaggi
Sabrina Strano
Giovanni Blandino
Gabriella D’Orazi
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-019-1302-0

Other articles of this Issue 1/2019

Journal of Experimental & Clinical Cancer Research 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine