A drug screen was performed by a joint study group at the Department of Urology led by Shahrokh Shariat and Walter Berger at MedUni Vienna's Center for Cancer Research in collaboration with the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Stefan Kubicek's working group). The effects of over 1,700 chemical compounds on 23 cell lines representing different stages and subtypes of bladder cancer were investigated. Thereby, the scientists were able to identify over 470 substances with inhibitory (growth-inhibiting) effects. These included a large number of drugs already used for cancers, but also medications for other disease, including drugs for the treatment of malaria, parasitic diseases and various mental disorders.
Leukaemia drug offers hope in urothelial carcinoma and sarcomatoid carcinoma
One of these compounds, clofarabine, an antimetabolite drug currently used as a treatment for childhood leukaemia, was studied in more detail. For this purpose, the researchers developed models from patient material representing different types of bladder cancer. Besides of "conventional" urothelial carcinoma, they were also able to establish an animal model for sarcomatoid carcinoma. This is a rare subtype of bladder cancer, for which there is currently no effective chemotherapy. "We found that clofarabine induced complete remission in mice with conventional urothelial carcinoma and massive, sustained tumour shrinkage in animals with sarcomatoid carcinoma, while not causing any apparent side effects," said first author Iris Ertl from the Department of Urology, describing the results.
Use in clinical trials for the treatment of metastatic bladder cancer
Next steps will be clinical trials in which patients with metastatic bladder cancer who, for various reasons, cannot receive cisplatin-based therapy, will be treated with clofarabine prior to radical cystectomy (surgical removal of the urinary bladder). Shahrokh Shariat explains: "Our discovery was made possible by the close interdisciplinary collaboration with CeMM and the Center of Cancer Research. We very much look forward to continuing to work with our partners to incorporate our findings into clinical practice."
Service: European Urology
Molecular and Pharmacological Bladder Cancer Therapy Screening: Discovery of Clofarabine as a Highly Active Compound
Iris E.Ertl, Ursula Lemberger, Dafina Ilijazi, Melanie R.Hassler, Andreas Bruchbacher, Robert Brettner, Hannah Kronabitter, Michael Gutmann, Petra Vician, Gerhard Zeitler, Anna Koren, Charles-Hugues Lardeau, Thomas Mohr, Andrea Haitel, Eva Compérat, André Oszwald, Gabriel Wasinger, Thomas Clozel, Olivier Elemento, Stefan Kubicek, Walter Berger, Shahrokh F. Shariat;
Eur Urol 2022 Apr 4;S0302-2838(22)01678-5. doi: 10.1016/j.eururo.2022.03.009.