Targeted therapies and biological modifiers in urologic tumors: pathobiology and clinical implications

Most conventional anticancer drugs act by preventing cells from dividing or have toxic effects on dividing cells, but the toxic effects on the normal cells in the body limit the dosage to a level below that which is effective for complete response. There has been a search for more specific agents that have a much greater effect on cancer, rather than on normal cells. Several new anticancer agents are in early development, and some are in clinical practice. Many of these new therapies require histological or molecular pathological testing to determine the therapy effectiveness. Aspects of the new targeted therapies for specific cancers are therefore of increasing relevance to both molecular and anatomic pathologists, including the biology behind, the eligibility criteria (by histology or molecular assays), specimen requirements, response assessment, and biologic or histological aspects of secondary resistance. Methodologies in this field are immunohistochemistry and fluorescent in situ hybridization, but PCR-based methods have great potential. The role of the pathologist in applying all of these new therapeutic targets to urologic tumors remains limited at present time, but in the future it should parallel their role for other cancers where targeted therapy has been more successful. The current status of biological and clinicopathological aspects of targeted therapy in prevalent urologic tumors is reviewed.