Urine-derived bladder cancer organoids (urinoids) as a tool for cancer longitudinal response monitoring and therapy adaptation

尿液来源的膀胱癌类器官(尿素)作为癌症纵向反应监测和治疗适应的工具

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作者:Bastiaan J Viergever, Daniëlle A E Raats, Veerle Geurts, Jasper Mullenders, Trudy N Jonges, Michiel S van der Heijden, Johan H van Es, Onno Kranenburg, Richard P Meijer

Background

Bladder cancer is one of the most common cancer types worldwide. Generally, research relies on invasive sampling strategies.

Conclusion

Therefore, urinoids can advance precision medicine in bladder cancer as a non-invasive platform for tumour pathogenesis, longitudinal drug-response monitoring, and therapy adaptation.

Methods

Here, we generate bladder cancer organoids directly from urine (urinoids). In this project, we establish 12 urinoid lines from 22 patients with non-muscle and muscle-invasive bladder tumours, with an efficiency of 55%.

Results

The histopathological features of the urinoids accurately resemble those of the original bladder tumours. Genetically, there is a high concordance of single nucleotide polymorphisms (92.56%) and insertions & deletions (91.54%) between urinoids and original tumours from patient 4. Furthermore, these urinoids show sensitivity to bladder cancer drugs, similar to their tissue-derived organoid counterparts. Genetic analysis of longitudinally generated tumoroids and urinoids from one patient receiving systemic immunotherapy, identify alterations that may guide the choice for second-line therapy. Successful treatment adaptation was subsequently demonstrated in the urinoid setting.

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