Our method uses clinical material obtained during surgery to derive mini tumours (organoids). Our protocol details the preparation of the organotypic medium required to support the growth of human bladder cancer organoids, as well as describing best practise approaches to dissociate the tumour tissue and ensure viable cells are retained for organoid growth.
Despite a growing interest in tailoring therapies to patients, current widely used in vitro therapeutic testing platforms, such as 2-dimensional culture of cell lines established many years ago, often lack direct relevance to tumour pathophysiology. The organoids generated using this protocol can be used as in vitro surrogates to elucidate the molecular mechanisms underpinning urological cancer pathology in addition to evaluating treatments to inform clinical management (Figure 1). This platform may be particularly useful to incorporate in companion studies for clinical trials investigating novel therapies for bladder cancer to establish their predictive relevance and to contextualise genomic analyses.
Bladder cancer organoids provide an opportunity to incorporate a personalized functional therapeutic screening approach into precision medicine healthcare models to further inform treatment selection and contribute to our understanding of the molecular mechanisms underpinning this disease and therapeutic responsiveness.
Figure 1. Bladder cancer organoids as precision medicine tools. Following standard cystectomy or trans urethral resection of bladder tumour (TURBT) procedures (1), tumour biopsies (2) from consented patients are excised and rapidly processed in the laboratory (3) for genomic sequencing (4) and organoid generation. Microscopic tumour aggregates dynamically remodel in vitro (5) to form viable bladder cancer organoids (6). Following genomic (4) and morphological (7) analyses, bladder cancer organoids are subjected to in vitro drug screening assays (8) with standard of care drugs and genomically-identified targeted therapies to determine drug sensitivity. Following integration of pharmacological responses with genomic analysis (9), the treatments most likely to be effective are identified (10) to improve outcomes for people with bladder cancer (11).
Written by:
- Elizabeth D. Williams, BSc(Hons), PhD, FFSc(RCPA), Queensland University of Technology, Brisbane, QLD, Australia
- Patrick Thomas, BAppSci(MedSci)(Hons), PhD, Queensland University of Technology, Brisbane, QLD, Australia
- Ian Vela, BSc, MBBS, PhD, FRACS(Urology), Princess Alexandra Hospital, Queensland University of Technology, Brisbane, QLD, Australia