LAUSR

Diverse clinical outcomes in bladder cancers result from varying molecular profiles. Shen and colleagues generated a biobank of patient-derived bladder cancer organoids to study tumour heterogeneity, evolution and drug responses. Organoid lines were established from 16 patients with lesions ranging from lowgrade, non-muscle-invasive disease to high-grade, muscle-invasive cancer, during different time points. Using orthotopic xenografts in immunodeficient mice, the authors could confirm similar histological and mutational profiles between organoids and primary tumours. Deep sequencing indicated that the tumour genotype was largely maintained in culture, although many organoids underwent clonal evolution during serial passaging. Interestingly, a tendency to transition to a basal phenotype was evident in culture, which was reversible in xenografts. Effects of 50 compounds with established relevance for bladder cancer were evaluated, with responses showing partial correlations with mutational profiles. Recurrent cancer organoids demonstrated resistance to a wider range of drugs. Based on the mutational profiles of these lines it was possible to predict drug responses, some of which were recapitulated in subsequent xenograft experiments. Overall the authors confirm the value and effectiveness of 3D bladder cancer organoids as preclinical models and for drug screening.