title: Current and emerging strategies in bladder cancer.
abstract: Urothelial cell carcinoma is one of the most common malignancies of the urinary tract. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease within 5 years. In the setting of muscle-invasive urothelial carcinoma, use of neoadjuvant chemotherapy is associated with overall survival benefit. Muscle invasive bladder cancer is life threatening, showing modest chemosensitivity, and usually requires radical cystectomy. Although bladder cancer is fairly well-genetically characterized, clinical trials with molecularly targeted agents have, in comparison to other solid tumors, been few in number and largely unsuccessful. Hence, bladder cancer represents a considerable opportunity and challenge for alternative therapies. In this review, we will focus on promising global or pathway-based approaches (epigenetic modulators, kinase inhibitors, angiogenesis blockage, peroxisome proliferator-activated receptor γ agonists, apoptosis inductors, virus therapy) supported by a deeper understanding of molecular biology of urothelial carcinoma, which have been recently tested in clinical trials.
authors: Dipartimento di Chimica e Tecnologie del Farmaco and Dipartimento di Scienze Ginecologico- Ostetriche e Scienze Urologiche, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. simone.carradori@uniroma1.it
authors: Simone
authors: S
authors: Carradori
authors: Cristiano
authors: C
authors: Cristini
authors: Daniela
authors: D
authors: Secci
authors: Caterina
authors: C
authors: Gulia
authors: Vincenzo
authors: V
authors: Gentile
authors: Giovanni Battista
authors: GB
authors: Di Pierro
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000819:agonists / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods*; D050130:Oncolytic Virotherapy / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D019459:Urothelium / Q000187:drug effects / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D051017:Apoptosis Regulatory Proteins; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases