Hundreds of chemical compounds were screened on cell cultures representing different stages and subtypes of bladder cancer and several promising agents with inhibitory (growth-inhibiting) effects were identified. A drug used to treat childhood leukaemia was found to have good efficacy in two specific types of bladder cancer. The study, which was conducted at MedUni Vienna, was recently published in the leading journal欧洲泌尿科。

Working in collaboration with the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences (Stefan Kubicek's working group), a joint study group at the Department of Urology led by Shahrokh Shariat and Walter Berger at MedUni Vienna's Center for Cancer Research screened various drugs. They investigated the effects of over 1,700 chemical compounds on 23 commercially available cell lines representing different stages and subtypes of bladder cancer. 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 and also drugs for treating malaria, parasitic diseases and various mental disorders, for example.

白血病药物在尿路上皮癌和肉瘤癌中提供希望

One of these compounds, clofarabine, an antimetabolite currently used as a treatment for childhood leukaemia, was studied in more detail. For this, the researchers developed models from patient material representing different types of bladder cancer. In addition to "conventional" urothelial carcinomas, 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, while in the animals with sarcomatoid carcinomas it led to massive, sustained shrinkage of the tumours without 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

下一步将是临床试验，其中转移性膀胱癌的患者因各种原因无法接受顺铂治疗，将在自由基膀胱切除术（手术切除膀胱）之前给予克拉法滨。Shahrokh Shariat解释说：“与CEMM和CEMM和癌症研究所的紧密跨学科合作使我们的发现成为可能。我们非常期待与我们的合作伙伴合作，将我们的发现纳入临床实践。”

参考：Ertl IE，Lemberger U，Ilijazi D等。分子和药理学膀胱癌疗法筛查：克洛法拉滨作为高活性化合物的发现。欧洲泌尿科。2022. doi:10.1016/j.eururo.2022.03.009

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