title: Cytotoxic and DNA-targeted therapy in urothelial cancer: have we squeezed the lemon enough?
abstract: Urothelial cancer has long been known as a chemotherapy-sensitive disease. However, clinical trial data to date suggest a plateau to the magnitude of benefit from cytotoxic therapy alone. In spite of level 1 evidence supporting cisplatin-based chemotherapy for patients with muscle-invasive and metastatic urothelial cancer, underuse prevails among patients with localized disease and only a modest survival benefit exists in the metastatic setting, although trials have consistently demonstrated that there is a subset of patients who clearly benefit. Recent comprehensive genomic profiling has identified a high prevalence of actionable genomic alterations as well as other potential targets yet to be fully understood. Modern clinical trials must now focus on identifying predictive biomarkers to select those patients who will benefit most from cytotoxic chemotherapy, molecularly targeted therapy, or potentially both.
authors.affiliation: Genitourinary Cancers Program, Perlmutter Cancer Center, NYU Langone Medical Center, New York, New York.
authors.forename: Arjun V
authors.initials: AV
authors.lastname: Balar
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D004273:DNA, Neoplasm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation / Q000187:drug effects; D020360:Neoadjuvant Therapy / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019459:Urothelium / Q000473:pathology*; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate
keywords: The Cancer Genome Atlas (TCGA); bladder cancer; chemotherapy; cisplatin; paclitaxel; predictive biomarkers; taxanes; urothelial cancer