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Metabolic modeling-based drug repurposing in Glioblastoma

Tomi-Andrino, Claudio; Pandele, Alina; Winzer, Klaus; King, John; Rahman, Ruman; Kim, Dong-Hyun

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Authors

Claudio Tomi-Andrino

Alina Pandele

JOHN KING JOHN.KING@NOTTINGHAM.AC.UK
Professor of Theoretical Mechanics



Abstract

The manifestation of intra- and inter-tumor heterogeneity hinders the development of ubiquitous cancer treatments, thus requiring a tailored therapy for each cancer type. Specifically, the reprogramming of cellular metabolism has been identified as a source of potential drug targets. Drug discovery is a long and resource-demanding process aiming at identifying and testing compounds early in the drug development pipeline. While drug repurposing efforts (i.e., inspecting readily available approved drugs) can be supported by a mechanistic rationale, strategies to further reduce and prioritize the list of potential candidates are still needed to facilitate feasible studies. Although a variety of ‘omics’ data are widely gathered, a standard integration method with modeling approaches is lacking. For instance, flux balance analysis is a metabolic modeling technique that mainly relies on the stoichiometry of the metabolic network. However, exploring the network’s topology typically neglects biologically relevant information. Here we introduce Transcriptomics-Informed Stoichiometric Modelling And Network analysis (TISMAN) in a recombinant innovation manner, allowing identification and validation of genes as targets for drug repurposing using glioblastoma as an exemplar.

Citation

Tomi-Andrino, C., Pandele, A., Winzer, K., King, J., Rahman, R., & Kim, D. (2022). Metabolic modeling-based drug repurposing in Glioblastoma. Scientific Reports, 12, Article 11189. https://doi.org/10.1038/s41598-022-14721-w

Journal Article Type Article
Acceptance Date Jun 10, 2022
Online Publication Date Jul 1, 2022
Publication Date Jul 1, 2022
Deposit Date Jun 28, 2022
Publicly Available Date Jul 4, 2022
Journal Scientific Reports
Electronic ISSN 2045-2322
Publisher Springer Science and Business Media LLC
Peer Reviewed Peer Reviewed
Volume 12
Article Number 11189
DOI https://doi.org/10.1038/s41598-022-14721-w
Keywords Multidisciplinary
Public URL https://nottingham-repository.worktribe.com/output/8764835
Publisher URL https://www.nature.com/articles/s41598-022-14721-w

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