Novel molecular targets for the therapy of urothelial carcinoma.

Introduction: First-line platinum-based combinations are active in locally advanced and metastatic urothelial carcinoma; however, long-term outcomes including disease-specific and overall survival remain suboptimal. In addition, approximately 40 - 50% of patients with advanced urothelial carcinoma have coexisting medical issues that preclude the use of cisplatin-based therapy. Improvements in our understanding of the molecular mechanisms of urothelial tumorigenesis have led to first-generation clinical trials evaluating novel agents targeting molecular pathways. These are particularly relevant in regard to subpopulations. Novel trial designs warrant consideration to accelerate accrual.

Areas Covered: In this review, novel molecular targets for the therapy of urothelial carcinoma, as well as recently completed and ongoing clinical trials utilizing novel targeted agents, are discussed. A Medline search with key words, abstracts reported at national conferences on urothelial carcinoma and NCI clinical trial identifiers was used for this review.

Expert Opinion: Improved understanding of molecular biology has identified a number of new molecular targets, but there is a seeming absence of one dominant molecular driver for urothelial cancer. An adaptive and biomarker-derived strategy may be warranted. Clinical trials utilizing targeted agents are ongoing and results are awaited.