A study performed at MedUni Vienna has discovered hundreds of new potential bladder cancer treatments, with one commonly used drug demonstrating effectiveness against two specific types of the disease.
The project, which comprised researchers from MedUni Vienna’s Center for Cancer Research and the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, screened hundreds of chemical compounds on cell cultures that represented various stages of subtypes of bladder cancer. The endeavour, led by Shahrokh Shariat and Walter Berger, found an array of promising bladder cancer treatments with growth-inhibiting properties, one being a drug already employed to treat childhood leukaemia.
The full findings of the research are published in the journal European Urology.
Identifying novel bladder cancer treatments
For their investigation, the researchers examined the performance of more than 1,700 chemical compounds on 23 commercially available cell lines that act as the different stages of multiple types of bladder cancer.
From this process, the scientists were able to distinguish over 470 substances that may be effective bladder cancer treatments, all of which had inhibitory effects. These compounds included a plethora of widely used drugs already implemented to combat other cancers, in addition to medications implemented for treating malaria, parasitic diseases, and various mental health disorders.
Repurposing leukaemia medication
Perhaps the most exciting compound the study achieved in identifying was clofarabine – an antimetabolite that is currently utilised as a treatment for childhood leukaemia. To study clofarabine further, the team developed models from patient material that represented different types of bladder cancer.
The team established ‘conventional’ urothelial carcinomas and also an animal model for sarcomatoid carcinoma – a particularly rare subtype of the disease for which there are currently no effective bladder cancer treatments, with chemotherapy not able to treat the condition.
Iris Ertl, the first author of the study from the Department of Urology, commented: “We found that clofarabine induced complete remission in mice with conventional urothelial carcinoma, while in the animals with sarcomatoid carcinomas, it led to massive, sustained shrinkage of the tumours without causing any apparent side effects.”
Next steps
The researchers are now planning to perform clinical trials where patients with metastatic bladder cancer that, for many reasons, cannot be administered cisplatin-based therapy will be given clofarabine before undergoing radical cystectomy, an operation in which the urinary bladder is removed through surgery.
Shahrokh Shariat concluded: “Our discovery was made possible by the close interdisciplinary collaboration with CeMM and the Institute of Cancer Research. We very much look forward to continuing to work with our partners to incorporate our findings into clinical practice.”
