Targeting Bladder Cancer Stem Cells: One Step Closer to the Clinic?

There is accumulating evidence supporting that the bladder urothelium contains self-renewing stem cells important for maintaining normal tissue homeostasis and injury response. It is therefore unsurprising that cancers arising from such hierarchically organized urothelial tissues retain features of cellular differentiation. Bladder cancer stem cells (CSCs) (or tumor-initiating cells) have been isolated and studied for their phenotypic and functional properties. Since these cells were demonstrated to be intrinsically resistant and could evade conventional cytotoxic chemotherapy, they become ideal targets for anticancer therapies. In the current book chapter, we will highlight the recent progress in the investigation of normal urothelial and neoplastic bladder stem cells. We will focus on prognostic developments using CSC (or differentiation) markers to subclassify bladder cancer into subtypes that correlate with clinical outcome, the contribution of cellular differentiation signaling pathways and their cross talk with the stromal microenvironment to drive different cancer subtypes, and finally, the clinical implications of targeting CSCs as the next generation anticancer therapy.