Bladder cancer and cancer stem cells: basic science and implications for therapy.

Bladder cancer is the fifth most common cancer in Western society, with the global burden predicted to increase significantly in the foreseeable future. Over 90% of these bladder cancers are transitional cell carcinomas of urothelial origin (urothelial carcinomas or UCs) and at presentation, over 70% will be non-muscle-invasive or stage Ta/T1 tumours, with the remainder being muscle-invasive or stages T2-4. Bladder UC is a highly heterogeneous disease: for the 50-55% of bladder cancer patients presenting with Ta tumours, recurrence is the main issue, but for the 20-25% of patients presenting with T1 tumours, progression is the main issue. Progression to, or presentation with, muscle-invasive disease represents the critical step for patients, necessitating more aggressive therapies and carrying significantly worse survival rates. We therefore urgently require detailed molecular insights into the pathogenesis of muscle-invasive bladder cancer so that the disease can be more adequately and appropriately treated at presentation, so that progression from stages Ta/T1 can be abrogated, and so that the risk of recurrence following treatment can be minimised. The recently identified bladder cancer stem cells are considered to be mediators of resistance to current therapies and therefore represent strong candidate biological targets. The aim of this review is to discuss the background and basic science of such cells, and the implications for current and future therapies.