The University of Southampton
University of Southampton Institutional Repository

Key players in the mutant p53 team: small molecules, gene editing, immunotherapy

Key players in the mutant p53 team: small molecules, gene editing, immunotherapy
Key players in the mutant p53 team: small molecules, gene editing, immunotherapy
The transcription factor p53 is a key tumor suppressor that is inactivated in almost all cancers due to either point mutations in the TP53 gene or overexpression of its negative regulators. The p53 protein is known as the “cellular gatekeeper” for its roles in facilitating DNA repair, cell cycle arrest or apoptosis upon DNA damage. Most p53 mutations are missense and result in either structural destabilization of the protein, causing its partial unfolding and deactivation under physiological conditions, or impairment of its DNA-binding properties. Tumor cells with p53 mutations are generally more immunogenic due to “hot spot” neoantigens that instigate the immune system response. In this review, we discuss the key therapeutic strategies targeting mutant p53 tumors, including classical approaches based on small molecule intervention and emerging technologies such as gene editing and T cell immunotherapy.
2234-943X
Chasov, Vitaly
65364491-ad64-46da-a303-ae6a63abd56e
Mirgayazova, Regina
fbe44855-d5cb-427b-b538-f9d84aa65ed5
Zmievskaya, Ekaterina
5dccac8d-a4c2-4c60-a873-4e1643c3564d
Khadiullina, Raniya
560b02a8-6381-4fb6-b359-5d020e76a675
Valiullina, Aygul
0cda654c-125d-4873-87a3-481c8e4e638f
Stephenson Clarke, Joseph Richard
f92a6e84-4929-4908-a88b-0522b1703916
Rizvanov, Albert
f0ada3be-27b9-4775-a487-defe497a33e9
Baud, Matthias G.J.
8752d519-3d33-43b6-9a77-ab731d410c2e
Bulatov, Emil
604a6ecd-d91c-42d2-bb16-0eb720b2b7b3
Chasov, Vitaly
65364491-ad64-46da-a303-ae6a63abd56e
Mirgayazova, Regina
fbe44855-d5cb-427b-b538-f9d84aa65ed5
Zmievskaya, Ekaterina
5dccac8d-a4c2-4c60-a873-4e1643c3564d
Khadiullina, Raniya
560b02a8-6381-4fb6-b359-5d020e76a675
Valiullina, Aygul
0cda654c-125d-4873-87a3-481c8e4e638f
Stephenson Clarke, Joseph Richard
f92a6e84-4929-4908-a88b-0522b1703916
Rizvanov, Albert
f0ada3be-27b9-4775-a487-defe497a33e9
Baud, Matthias G.J.
8752d519-3d33-43b6-9a77-ab731d410c2e
Bulatov, Emil
604a6ecd-d91c-42d2-bb16-0eb720b2b7b3

Chasov, Vitaly, Mirgayazova, Regina, Zmievskaya, Ekaterina, Khadiullina, Raniya, Valiullina, Aygul, Stephenson Clarke, Joseph Richard, Rizvanov, Albert, Baud, Matthias G.J. and Bulatov, Emil (2020) Key players in the mutant p53 team: small molecules, gene editing, immunotherapy. Frontiers in Oncology, 10, [1460]. (doi:10.3389/fonc.2020.01460).

Record type: Review

Abstract

The transcription factor p53 is a key tumor suppressor that is inactivated in almost all cancers due to either point mutations in the TP53 gene or overexpression of its negative regulators. The p53 protein is known as the “cellular gatekeeper” for its roles in facilitating DNA repair, cell cycle arrest or apoptosis upon DNA damage. Most p53 mutations are missense and result in either structural destabilization of the protein, causing its partial unfolding and deactivation under physiological conditions, or impairment of its DNA-binding properties. Tumor cells with p53 mutations are generally more immunogenic due to “hot spot” neoantigens that instigate the immune system response. In this review, we discuss the key therapeutic strategies targeting mutant p53 tumors, including classical approaches based on small molecule intervention and emerging technologies such as gene editing and T cell immunotherapy.

Text
FINAL 040720 Manuscript mb eb - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (306kB)
Text
key players - Version of Record
Available under License Creative Commons Attribution.
Download (1MB)

More information

Accepted/In Press date: 9 July 2020
e-pub ahead of print date: 18 August 2020
Published date: August 2020

Identifiers

Local EPrints ID: 444147
URI: http://eprints.soton.ac.uk/id/eprint/444147
ISSN: 2234-943X
PURE UUID: fc05794f-4d0e-4301-8260-dd59ba0fc07a
ORCID for Matthias G.J. Baud: ORCID iD orcid.org/0000-0003-3714-4350

Catalogue record

Date deposited: 29 Sep 2020 17:33
Last modified: 07 Oct 2020 02:09

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×