Innovative Molecular Therapeutic Approaches in Urothelial Carcinoma

In the review, Antibody-drug conjugates and predictive biomarkers in advanced urothelial carcinoma, the authors discuss several ADCs that are currently being studied in UCC. The review includes an informative and thorough list of ongoing ADC trials in UCC. Furthermore, the authors discuss potential biomarkers for targeted therapy in UCC, including nectin-4, TP53, CDKN2B, Trop-2, Topoisomeraise-1, and HER2.Of the ADCs being evaluated in UCC, enfortumab-vedotin (EV) is the most used. In Enfortumab vedotin in metastatic urothelial carcinioma: the solution EVentually, the authors provide an in-depth examination of the activity of EV in metastatic UCC. In the review, readers will learn the pharmacology, pertinent completed clinical trials, placement of treatment with EV relative to other approved therapies, safety signals, and management of adverse effects. A very useful table of current, open EV studies is also included. This review of EV in metastatic UC is particularly timely given the recent data showing EV in combination with pembrolizumab to be superior to platinum-based chemotherapy in patients with metastatic UCC(3).While targeting HER2 in UCC is not new, to date it has met with mixed results. In HER2 expression in urothelial carcinoma, a systemic literature review, the authors seek to determine the prevalence of HER2 expression in UCC from the published body of literature. The analysis includes a modern classification: HER2 positive, HER2 low, and HER2 negative. Additional important considerations assessed are the method of HER2 evaluation (expression, gene amplification, or mutation), and concordance of different testing methods.The Research Topic considers narrower scopes of investigation within different types of UCC. Intravesical instillation of Bacillus Calmette-Guerin (BCG) is commonly used to treat nonmuscle invasive UCC. In the original article, Antibiotic therapy impact on intravesical BCG therapy efficacy for high-risk localized bladder cancer treatment, the authors perform a retrospective analysis to determine the degree to which antibiotic use affects the efficacy of BCG. Consideration is given to duration or delay of treatment, and effects on recurrence and progression.Upper tact UCC is often treated similarly to bladder UCC, but the development of targeted therapies in upper tract UCC is even more scarce than in bladder UCC. In Clinicopathological characteristics and loss of mismatch repairer protein expression in Chinese upper tract urothelial carcinomas the authors explore the implications of loss of DNA mismatch repair functionality in a Chinese cohort of patients. Rates of mismatch repair (MMR) loss, and the effects on T-stage and survival are examined. Comparison is also made to a Western cohort.The Research Topic is completed with an assessment of fibroblast growth factor receptor (FGFR) targeted therapy in metastatic UCC. The FGFR inhibitor, erdafitinib, is active in FGFR altered metastatic UCC(4). In Erdafitinib treatment in metastatic urothelial carcinoma: a realworld analysis, the authors report the clinical benefit and safety profile of erdafitinib in a realworld setting.In the Research Topic, Innovative Molecular Therapeutic Approaches in Urothelial Carcinoma we provide pertinent articles examining ADCs, HER2, FGFR, MMR, and the effect of antibiotic use in UCC. As laboratory researchers and clinical investigators increase focus on molecularly targeted therapies, we will find more efficacious and tolerable therapies for UCC.