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Updated: Nov 28, 2025
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients' Omics Signatures
Marika Mokou1,2, Vasiliki Lygirou1, Ioanna Angelioudaki1
1Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
Abstract:
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.
Insights
This study identifies WYE-354, an mTOR inhibitor, as a potential drug repurposing candidate for bladder cancer (BC). It uses multi-omics signatures to reverse aggressive BC molecular subtypes, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Genomics
Background:
- Bladder cancer (BC) drug discovery can benefit from repurposing existing therapeutics.
- Multi-omics signatures offer a novel approach to identify targeted therapies for BC subtypes.
Purpose of the Study:
- To leverage patient tissue omics signatures for drug repurposing in bladder cancer.
- To identify compounds capable of reversing aggressive high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) molecular subtypes to less aggressive ones.
Main Methods:
- Utilized the next-generation Connectivity Map (CMap) database.
- Input included previously published proteomics and transcriptomics signatures from BC patients.
- Assessed the impact of identified compounds on BC cell lines.
Main Results:
- The mTOR inhibitor WYE-354 demonstrated a high score for reversing aggressive BC molecular signatures.
- WYE-354 impaired colony growth and proliferation in a panel of eight BC cell lines.
- No significant impact on apoptosis was observed for WYE-354.
Conclusions:
- Introduced a novel drug repurposing pipeline for bladder cancer based on patient omics signatures.
- WYE-354 is a promising candidate for repositioning as a bladder cancer therapeutic.
- This approach facilitates the identification of de-risked therapeutic compounds for BC treatment.
