Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer

Horst, Geertje van der; Merbel, A.F. van de; Ruigrok, Eline A. M.; Mark, Maaike H. van der; Ploeg, Emily M.; Appelman, L.M.; Tvingsholm, Siri Amanda; Jäätelä, Marja; Uhm, Janneke van; Julio, Marianna Kruithof-de; Thalmann, George N.; Pelger, Rob C.M.; Bangma, Chris H.; Boormans, Joost L.; Pluijm, Gabri van der; Zwarthoff, Ellen C.

doi:10.1002/1878-0261.12793

Cited by 8 publications

(2 citation statements)

References 34 publications

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“…Drug repurposing is considered a promising approach [21], accelerating transfer to the clinic and reducing costs in comparison to de novo drug discovery [22]. In the context of BC, drug repurposing was adopted for use of cationic amphiphilic drugs, a class of commonly used antidepressants, antihistamines and antipsychotics drugs, that demonstrated an antineoplastic efficacy in BC cell lines, in a human orthotopic BC xenograft model and ex vivo in patient-derived tissues [23]. In this case, repurposing was based on evaluation of retrospective/observational studies providing evidence that the incidence of BC in patients with schizophrenia was significantly lower in comparison to individuals without schizophrenia [23].…”

Section: Discussionmentioning

confidence: 99%

“…In the context of BC, drug repurposing was adopted for use of cationic amphiphilic drugs, a class of commonly used antidepressants, antihistamines and antipsychotics drugs, that demonstrated an antineoplastic efficacy in BC cell lines, in a human orthotopic BC xenograft model and ex vivo in patient-derived tissues [23]. In this case, repurposing was based on evaluation of retrospective/observational studies providing evidence that the incidence of BC in patients with schizophrenia was significantly lower in comparison to individuals without schizophrenia [23]. Along the same lines, the repurposing potential of Nitazoxanide, a cysticidal drug with immuno-anticarcinogenic action, was investigated in a NMIBC animal model and showed therapeutic potential when used simultaneously with BCG treatment [24].…”

Section: Discussionmentioning

confidence: 99%

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A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients’ Omics Signatures

Mokou

Lygirou

Angelioudaki

et al. 2020

Cancers

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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.

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Section: Discussionmentioning

confidence: 99%