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

Author:

Viergever Bastiaan1ORCID,Raats Daniëlle1,Geurts Veerle2,Mullenders Jasper2,Jonges Trudy3,Heijden Michiel (S.) Van der4ORCID,Es Johan van2,Kranenburg Onno1ORCID,Meijer Richard1ORCID

Affiliation:

1. University Medical Center Utrecht

2. Hubrecht Institute

3. Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht

4. NKI

Abstract

Abstract Bladder cancer is one of the most common cancer-types worldwide. Generally, research relies on invasive sampling strategies. 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 tumors, with an efficiency of 55%. The histopathological features of the urinoids accurately resemble those of the original bladder tumors. Genetically there is a high concordance of single nucleotide polymorphisms (92.56%) and insertions and deletions (91.54%) between urinoids and original tumors. Furthermore, urinoids show sensitivity to bladder cancer drugs, similar to their tissue-derived organoid counterparts. Genetic analysis of longitudinally generated 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. Therefore, urinoids can advance precision medicine in bladder cancer as a non-invasive platform for tumor pathogenesis, longitudinal drug-response monitoring, and therapy adaptation.

Publisher

Research Square Platform LLC

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