Novel agents in invasive urothelial cancer

Invasive urothelial cancer is an aggressive, biologically heterogeneous disease. Most patients present with non-muscle invasive bladder cancer involving the epithelium as exophytic tumors, in situ carcinoma, or minimally invasive disease involving the lamina propria. Such patients are typically managed with complete transurethral resection with or without intravesical therapy. Muscle invasive urothelial cancer, however, is biologically and clinically distinct. This subtype is characterized by mutations or deletions in tumor suppressor genes, such as TP53, Rb, and PTEN, leading to genomic instability and a more aggressive phenotype. Survival in advanced disease is poor with currently available treatment strategies. Technological advances in the ability to molecularly characterize human cancer have led to the identification of genetic alterations that may be therapeutically exploitable. Novel chemotherapies, such as antifolates and taxanes, have shown promise in urothelial cancer. Agents against novel molecular targets, such as the human epidermal receptor (HER) and vascular endothelial growth factor receptor (VEGFR), are being investigated. This review article focuses on the current status of novel chemotherapeutic and targeted agents as well as immunotherapy currently in clinical development in invasive urothelial cancer.