A novel pipeline for drug repurposing for bladder cancer based on patients’ omics signatures

Mokou, M. et al. (2020) A novel pipeline for drug repurposing for bladder cancer based on patients’ omics signatures. Cancers, 12(12), 3519. (doi: 10.3390/cancers12123519) (PMID:33255925) (PMCID:PMC7759896)

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Multi-omics signatures of patients with bladder cancer (BC) can guide the identification of known de-risked therapeutic compounds through drug repurposing, an approach not extensively explored yet. In this study, we target drug repurposing in the context of BC, driven by tissue omics signatures. To identify compounds that can reverse aggressive high-risk Non-Muscle Invasive BC (NMIBC) to less aggressive low-risk molecular subtypes, the next generation Connectivity Map (CMap) was employed using as input previously published proteomics and transcriptomics respective signatures. Among the identified compounds, the ATP-competitive inhibitor of mTOR, WYE-354, showed a consistently very high score for reversing the aggressive BC molecular signatures. WYE-354 impact was assessed in a panel of eight multi-origin BC cell lines and included impaired colony growth and proliferation rate without any impact on apoptosis. Overall, with this study we introduce a promising pipeline for the repurposing of drugs for BC treatment, based on patients’ omics signatures.

Item Type:Articles
Additional Information:This work has received in part funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 898260 (H2020-MSCA-IF-2019, ReDrugBC, Grant agreement ID: 898260).
Keywords:Bladder cancer, drug repurposing, CMap, omics, proteomic, signature, NMIBC subtypes, MIBC, urothelial cell carcinoma cell lines, mTOR inhibitors.
Glasgow Author(s) Enlighten ID:Mischak, Professor Harald
Creator Roles:
Mischak, H.Conceptualization, Writing – original draft, Writing – review and editing, Supervision, Project administration, Funding acquisition
Authors: Mokou, M., Lygirou, V., Angelioudaki, I., Paschalidis, N., Stroggilos, R., Frantzi, M., Latosinska, A., Bamias, A., Hoffmann, M. J., Mischak, H., and Vlahou, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Cancers
ISSN (Online):2072-6694
Published Online:26 November 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Cancers 12(12): 3519
Publisher Policy:Reproduced under a Creative Commons License

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