A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.
RNA-seq
RNAi
attractors
clinical trial
drug repurposing
hubs
in vivo validation
interactome
tumor on a chip
tumors
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
08 Nov 2023
08 Nov 2023
Historique:
received:
23
07
2023
revised:
04
09
2023
accepted:
12
09
2023
medline:
27
11
2023
pubmed:
25
11
2023
entrez:
25
11
2023
Statut:
epublish
Résumé
We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.
Identifiants
pubmed: 38003288
pii: ijms242216098
doi: 10.3390/ijms242216098
pmc: PMC10671768
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Brazilian government (Fiocruz)
ID : No grant number
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