Understanding the biology of urothelial cancer metastasis

Management of unresectable urothelial cancer (UC) has been a clinical challenge for decades. While drug resistance is a key issue, precise understanding of biology of UC metastasis is another challenge for the improvement of treatment outcome of UC patients. Introduction of the cell biology concepts including epithelial-mesenchymal transition (EMT) and cancer stemness seems to explain UC metastasis. Molecular genetics based on gene expression profiling, next generation sequencing, and explosion of non-coding RNA world has opened the door to intrinsic molecular subtyping of UC. Next steps include, based on the recently accumulated understanding, the establishment of novel disease models representing UC metastasis in various experimental platforms, particularly in vivo animal systems. Indeed, novel knowledge molecular genetics has not been fully linked to the modeling of UC metastasis. Further understanding of bladder carcinogenesis is needed particularly with regard to cell of origin related to tumor characteristics including driver gene alterations, pathological differentiations, and metastatic ability. Then we will be able to establish better disease models, which will consequently lead us to further understanding of biology and eventually the development of novel therapeutic strategies for UC metastasis.