Molecular biology of urothelial cancer

Urothelial Carcinoma (UCa) is the commonest form of bladder cancer in the industrialized and western world, accounting for over ninety percent of all cases. In an attempt to broaden our understanding of the underlying pathology of UCa, herein, we have discussed the molecular signatures that characterize these lesions. While some of the genetic alterations that have been identified in bladder cancer, it is primarily seen in either low-grade or in high-grade disease, most changes tend to show considerable overlap. We have therefore utilized a pathway approach to emphasize common molecular alterations. These comprise signaling through fibroblast growth factor receptor 3 (FGFR3), the RAS oncogenes, the ErbB family of receptor tyrosine kinases (including the epidermal growth factor receptor and HER2/neu), the Phosphatidylinositol 3 Kinase Signaling Cascade, p53 and Retinoblastoma tumor suppressors as well as chromosome 9 alterations. We have collated data primarily from clinical studies and where relevant, in vitro studies and studies conducted in transgenic mouse models. Where possible, we have underscored potential clinical applications in terms of diagnosis, therapy and response to therapy and have highlighted newer avenues of research as well as some of the challenges moving forward.