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Active repurposing of drug candidates for melanoma based on GWAS, PheWAS and a wide range of omics data

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...

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Detalles Bibliográficos
Autores principales: Khosravi, Ali, Jayaram, B., Goliaei, Bahram, Masoudi-Nejad, Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584997/
https://www.ncbi.nlm.nih.gov/pubmed/31221082
http://dx.doi.org/10.1186/s10020-019-0098-x
Descripción
Sumario: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.