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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
University of Thessalia, Department of Urology, Larissa, Greece.
Ioannis
I
Zachos
Panagiotis A
PA
Konstantinopoulos
Vassilios
V
Tzortzis
Stavros
S
Gravas
Anastasios
A
Karatzas
Michalis V
MV
Karamouzis
Michael
M
Melekos
Athanasios G
AG
Papavassiliou
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors