Active repurposing of drug candidates for melanoma based on GWAS, PheWAS and a wide range of omics data.
Drug repurposing
Drug response
GWAS
Medical dermatology
Melanoma
Metabolomics
Oncology
PheWAS
Transcriptomic
Journal
Molecular medicine (Cambridge, Mass.)
ISSN: 1528-3658
Titre abrégé: Mol Med
Pays: England
ID NLM: 9501023
Informations de publication
Date de publication:
20 06 2019
20 06 2019
Historique:
received:
03
02
2019
accepted:
05
06
2019
entrez:
22
6
2019
pubmed:
22
6
2019
medline:
23
6
2020
Statut:
epublish
Résumé
Drug repurposing is a swift, safe, and cheap drug discovery method. Melanoma disorders present low survival and high mortality rates and are challenging to diagnose and treat. Moreover, there is a high volume of worldwide investigations that are attempting to find melanoma-related genes of influence, which can be identified as responsive targets for reliable treatment. In this study, we used a wide range of data analyses to analyze over 1100 genes and proteins of influence with respect to cutaneous malignant melanoma. Our analysis included various investigational results from genome- and phenome-wide association studies (GWAS and PheWAS, respectively), biomedical, transcriptomic, and metabolomic datasets. We then researched the DrugBank for potential melanoma targets from the selected list. We excluded known melanoma targets to obtain a list of druggable proteins. We performed a precise analysis of the drugs' pathogenesis and checked the expression profiles of the selected drugs having high associations with known anti-melanoma drugs. We found 35 drugs that interacted with 20 unique targets. These drugs appear to have high melanoma treatment potentials. We confirmed our results with previous studies and found supporting references for 30 of these drugs. In conclusion, this investigation can be applied to various diseases for the efficient and economical repurposing of various drug compounds. For further validation, the results may be applicable for in vivo tests and clinical trials.
Sections du résumé
BACKGROUND
Drug repurposing is a swift, safe, and cheap drug discovery method. Melanoma disorders present low survival and high mortality rates and are challenging to diagnose and treat. Moreover, there is a high volume of worldwide investigations that are attempting to find melanoma-related genes of influence, which can be identified as responsive targets for reliable treatment.
METHOD
In this study, we used a wide range of data analyses to analyze over 1100 genes and proteins of influence with respect to cutaneous malignant melanoma. Our analysis included various investigational results from genome- and phenome-wide association studies (GWAS and PheWAS, respectively), biomedical, transcriptomic, and metabolomic datasets. We then researched the DrugBank for potential melanoma targets from the selected list. We excluded known melanoma targets to obtain a list of druggable proteins. We performed a precise analysis of the drugs' pathogenesis and checked the expression profiles of the selected drugs having high associations with known anti-melanoma drugs.
RESULT
We found 35 drugs that interacted with 20 unique targets. These drugs appear to have high melanoma treatment potentials. We confirmed our results with previous studies and found supporting references for 30 of these drugs. In conclusion, this investigation can be applied to various diseases for the efficient and economical repurposing of various drug compounds. For further validation, the results may be applicable for in vivo tests and clinical trials.
Identifiants
pubmed: 31221082
doi: 10.1186/s10020-019-0098-x
pii: 10.1186/s10020-019-0098-x
pmc: PMC6584997
doi:
Substances chimiques
Biomarkers
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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