Novel agents in invasive urothelial cancer.
Invasive urothelial cancer is an aggressive, biologically heterogeneous disease. Most patients present with non-muscle invasive bladder cancer involving the epithelium as exophytic tumors, in situ carcinoma, or minimally invasive disease involving the lamina propria. Such patients are typically managed with complete transurethral resection with or without intravesical therapy. Muscle invasive urothelial cancer, however, is biologically and clinically distinct. This subtype is characterized by mutations or deletions in tumor suppressor genes, such as TP53, Rb, and PTEN, leading to genomic instability and a more aggressive phenotype. Survival in advanced disease is poor with currently available treatment strategies. Technological advances in the ability to molecularly characterize human cancer have led to the identification of genetic alterations that may be therapeutically exploitable. Novel chemotherapies, such as antifolates and taxanes, have shown promise in urothelial cancer. Agents against novel molecular targets, such as the human epidermal receptor (HER) and vascular endothelial growth factor receptor (VEGFR), are being investigated. This review article focuses on the current status of novel chemotherapeutic and targeted agents as well as immunotherapy currently in clinical development in invasive urothelial cancer.
Memorial Sloan-Kettering Cancer Center, New York, New York.
Arjun V
AV
Balar
Matthew I
MI
Milowsky
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human