Preclinical models of bladder cancer: BBN and beyond

Preclinical modelling is a crucial component of advancing the understanding of cancer biology and therapeutic development. Several models exist for understanding the pathobiology of bladder cancer and evaluating therapeutics. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder cancer is a commonly used model that recapitulates many of the features of human disease. Particularly in mice, BBN is a preferred laboratory model owing to a high level of reproducibility, high genetic fidelity to the human condition, and its relative ease of use. However, important aspects of the model are often overlooked in laboratory studies. Moreover, the advent of new models has yielded a variety of methodologies that complement the use of BBN. Toxicokinetics, histopathology, molecular genetics and sex can differ between available models and are important factors to consider in bladder cancer modelling. In this Review, the authors comprehensively assess current models of bladder cancer with an emphasis on the N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced bladder cancer model owing to its high fidelity to the human condition.