Molecular targets and targeted therapies in bladder cancer management.

ABSTRACT

Bladder cancer remains a significant health problem. Currently, conventional histopathologic evaluation criteria (tumor grade and stage) are limited in their ability to accurately predict tumor behavior. A significant number of patients with muscle-invasive or extravesical disease treated by radical cystectomy alone die of metastasis. Intense research efforts are being made to better identify and categorize tumors by their molecular alterations and biological characteristics. A majority of the aggressive, invasive bladder carcinomas have alterations in the p53 and retinoblastoma pathways that regulate the cell cycle by interacting with signal transduction pathways. Angiogenesis further contributes to the neoplastic growth by providing a constant supply of oxygen and nutrients. It is becoming apparent that the accumulation of genetic and molecular changes ultimately determines a tumor's phenotype and subsequent clinical behavior. We provide a contemporary outline of our current understanding of the molecular and genetic events associated with tumorigenesis and progression. We emphasize the ways by which molecular biology is likely to affect the development of future therapies that will be able to target molecular alterations in individual tumors based on their respective profiles. The current status of targeted therapies for bladder cancer is also presented as well as the ongoing clinical trials.