Urothelial cancer organoids: atool for bladder cancer research.

R. P. Meijer

doi:10.1007/s00292-021-00988-9

Abstract

BackgroundBladder cancer ranks among the top ten most common tumor types worldwide and represents a growing healthcare problem, accounting for a large part of total healthcare costs. Chemotherapy is effective in a subset of patients, while causing severe side effects. Tumor pathogenesis and drug resistance mechanisms are largely unknown. Precision medicine is failing in bladder cancer, as bladder tumors are genetically and molecularly very heterogeneous. Currently, therapeutic decision-making depends on assessing a single fragment of surgically acquired tumor tissue.ObjectiveNew preclinical model systems for bladder cancer are indispensable for developing therapeutic strategies tailored to individual patient and tumor characteristics. Organoids are small 3D tissue cultures that simulate small-size organs “in a dish” and tumoroids are a special type of cancer organoid (i.e., malignant tissue).Materials and methodsSince 2016, we have collaborated with the renowned Hubrecht Institute to provide proof of concept of tissue-based bladder tumoroids mimicking parental tumors. We have developed a living biobank containing bladder organoids and tumoroids grown from over 50 patient samples, which reflect crucial aspects of bladder cancer pathogenesis.ResultsHistological and immunofluorescence analysis indicated that the heterogeneity and subclassification of tumoroids mimicked those of corresponding parental tumor samples. Thus, urothelial tumoroids mimic crucial aspects of bladder cancer pathogenesis.ConclusionResearch with urothelial tumoroids will open up new avenues for bladder cancer pathogenesis and drug-resistance research as well as for precision medicine approaches.

Highlights

Bladder cancer ranks amongst the top five and top ten of the most common cancers in men and women, respectively [1]
Over 6500 patients were diagnosed with bladder cancer in the Netherlands in 2018
Multimodality treatment consisting of neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy or radiation therapy has been shown to improve the outcome of this high-risk group of patients with muscle-invasive bladder cancer, albeit at best a 6.5% increase in overall survival at 5-year follow-up [2, 7, 8]

Summary

Introduction

Bladder cancer ranks amongst the top five and top ten of the most common cancers in men and women, respectively [1]. Over 6500 patients were diagnosed with bladder cancer in the Netherlands in 2018. Bladder cancer patients are usually diagnosed through biopsies obtained by a cystoscope entering the bladder through the urethra. Despite improved anatomical knowledge and refinement of surgical techniques, approximately 40–50% of non-metastatic muscle-invasive bladder cancers develop local relapse and/or metastatic disease, with a poor and unchanged outcome over the past 25 years (5-year survival of muscle-invasive bladder cancer, including metastatic disease, is approximately 35%) [6]. Multimodality treatment consisting of neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy or radiation therapy has been shown to improve the outcome of this high-risk group of patients with muscle-invasive bladder cancer, albeit at best a 6.5% increase in overall survival at 5-year follow-up [2, 7, 8]. Evaluation of tumor biology and assessment of chemosensitivity of the individual bladder tumor is needed to guide personalized bladder cancer treatment [9, 10]

Pathogenesis of bladder cancer

Conclusion

Corresponding address

Findings

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