Drugging p53 in cancer: one protein, many targets.
Journal
Nature reviews. Drug discovery
ISSN: 1474-1784
Titre abrégé: Nat Rev Drug Discov
Pays: England
ID NLM: 101124171
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
accepted:
06
09
2022
pubmed:
11
10
2022
medline:
8
2
2023
entrez:
10
10
2022
Statut:
ppublish
Résumé
Mutations in the TP53 tumour suppressor gene are very frequent in cancer, and attempts to restore the functionality of p53 in tumours as a therapeutic strategy began decades ago. However, very few of these drug development programmes have reached late-stage clinical trials, and no p53-based therapeutics have been approved in the USA or Europe so far. This is probably because, as a nuclear transcription factor, p53 does not possess typical drug target features and has therefore long been considered undruggable. Nevertheless, several promising approaches towards p53-based therapy have emerged in recent years, including improved versions of earlier strategies and novel approaches to make undruggable targets druggable. Small molecules that can either protect p53 from its negative regulators or restore the functionality of mutant p53 proteins are gaining interest, and drugs tailored to specific types of p53 mutants are emerging. In parallel, there is renewed interest in gene therapy strategies and p53-based immunotherapy approaches. However, major concerns still remain to be addressed. This Review re-evaluates the efforts made towards targeting p53-dysfunctional cancers, and discusses the challenges encountered during clinical development.
Identifiants
pubmed: 36216888
doi: 10.1038/s41573-022-00571-8
pii: 10.1038/s41573-022-00571-8
pmc: PMC9549847
doi:
Substances chimiques
Tumor Suppressor Protein p53
0
Transcription Factors
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
127-144Informations de copyright
© 2022. Springer Nature Limited.
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