Systemic therapy of metastatic bladder cancer in the molecular era: current status and future promise

Importance of the field: Platinum-based chemotherapy is considered the standard-of-care first-line therapy for metastatic bladder cancer. Despite the initial high response rate, the vast majority of patients eventually progress and succumb to their disease, urging the need for development of novel therapies. Areas covered in this review: This article discusses the main signaling pathways implicated in the pathogenesis of bladder carcinomas, reviews recently completed and ongoing clinical trials, and anticipates the future direction of molecularly targeted agents. What the reader will gain: This manuscript presents the current status of conventional chemotherapy in advanced bladder cancer, and provides a comprehensive review of molecular targeted agents currently in clinical development for this disease. Take home message: Improved understanding of the biology of urothelial carcinogenesis has paved the way for the development of novel molecularly targeted therapies, several of which are currently tested in clinical trials. In this regard, VEGF and EGFR pathways are emerging as important therapeutic targets for metastatic bladder cancer, either alone or in combination with conventional chemotherapeutics. Other therapies, including aurora kinase inhibitors, endothelin receptor antagonists, RAS/MAPK pathway inhibitors and novel immunologic strategies, may also prove helpful in the treatment of this disease.