From GWAS to drug screening: repurposing antipsychotics for glioblastoma.
J Transl Med
; 20(1): 70, 2022 02 04.
Article
em En
| MEDLINE
| ID: mdl-35120529
ABSTRACT
BACKGROUND:
Glioblastoma is currently an incurable cancer. Genome-wide association studies have demonstrated that 41 genetic variants are associated with glioblastoma and may provide an option for drug development.METHODS:
We investigated FDA-approved antipsychotics for their potential treatment of glioblastoma based on genome-wide association studies data using a 'pathway/gene-set analysis' approach.RESULTS:
The in-silico screening led to the discovery of 12 candidate drugs. DepMap portal revealed that 42 glioma cell lines show higher sensitivities to 12 candidate drugs than to Temozolomide, the current standard treatment for glioblastoma.CONCLUSION:
In particular, cell lines showed significantly higher sensitivities to Norcyclobenzaprine and Protriptyline which were predicted to bind targets to disrupt a certain molecular function such as DNA repair, response to hormones, or DNA-templated transcription, and may lead to an effect on survival-related pathways including cell cycle arrest, response to ER stress, glucose transport, and regulation of autophagy. However, it is recommended that their mechanism of action and efficacy are further determined.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antipsicóticos
/
Neoplasias Encefálicas
/
Glioblastoma
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article