Cancer therapeutic targeting using mutant-p53-specific siRNAs.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
29
05
2018
accepted:
08
12
2018
revised:
29
11
2018
pubmed:
16
1
2019
medline:
22
5
2019
entrez:
16
1
2019
Statut:
ppublish
Résumé
Mutations in Tp53 compromise therapeutic response, due either to the dominant-negative effect over the functional wild-type allele; or as a result of the survival advantage conferred by mutant p53 to which cancer cells become addicted. Thus, targeting mutant p53 represents an effective therapeutic strategy to treat over half of all cancers. We have therefore generated a series of small-interfering-RNAs, capable of targeting four p53 hot-spot mutants which represent ~20% of all p53 mutations. These mutant-p53-specific siRNAs (MupSi) are highly specific in silencing the expression of the intended mutants without affecting wild-type p53. Functionally, these MupSis induce cell death by abrogating both the addiction to mutant p53 and the dominant-negative effect; and retard tumor growth in xenografts when administered in a therapeutic setting. These data together demonstrate the possibility of targeting mutant p53 specifically to improve clinical outcome.
Identifiants
pubmed: 30643191
doi: 10.1038/s41388-018-0652-y
pii: 10.1038/s41388-018-0652-y
pmc: PMC6756012
doi:
Substances chimiques
RNA, Small Interfering
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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