Network-based drug repurposing for multiple myeloma using saverunner in R
Background: Multiple myeloma (MM) remains a lethal blood malignancy, so new drugs are necessary in order to treat this cancer more effectively. Different types of in silico analyses make it possible to repurpose currently available drugs to diseases other than those they were originally designed for...
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| Format: | master thesis |
| Publication Date: | 2022 |
| Country: | España |
| Institution: | Universitat Oberta de Catalunya (UOC) |
| Repository: | O2, repositorio institucional de la UOC |
| OAI Identifier: | oai:openaccess.uoc.edu:10609/140506 |
| Online Access: | http://hdl.handle.net/10609/140506 |
| Access Level: | Open access |
| Keyword: | reutilització de fàrmacs mieloma múltiple càncer reutilización de fármacos cáncer drug repurposing multiple myeloma cancer Multiple myeloma -- TFM Mieloma múltiple -- TFM |
| Summary: | Background: Multiple myeloma (MM) remains a lethal blood malignancy, so new drugs are necessary in order to treat this cancer more effectively. Different types of in silico analyses make it possible to repurpose currently available drugs to diseases other than those they were originally designed for, with network-based analyses being a commonly chosen approach. Methodology: In this work, a drug repurposing study for MM was carried out by implementing in R the recently published algorithm SAveRUNNER, which performs network-based analyses to generate lists of potentially repurposable candidates for diseases of interest. Among the candidates to repurpose to MM suggested by SAveRUNNER, only those validated by differential gene expression analyses in MM samples followed by CMap queries were considered as most promising. Results: A final list of 22 drugs for MM repositioning belonging to different categories, such as enzyme inhibitors or steroids, was obtained, with many of them being already used to treat other types of cancers. Finally, molecular docking analyses of the potentially repurposable candidates ponatinib or axitinib with the KIT protein, overexpressed in MM according to this study, are presented to compare affinities of a protein for drugs of the same type in order to assess which would be preferable if included in a potential line of MM treatment. Conclusion: This study shows the accuracy of SAveRUNNER by suggesting drugs currently used to treat MM, and suggests new candidates for repositioning that may improve MM's current poor prognosis. |
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