Role of Targeted Therapies in Management of Metastatic Urothelial Cancer in the Era of Immunotherapy

Opinion statementDespite significant advances and the approval of immune checkpoint inhibitors, metastatic urothelial carcinoma (mUC) is still very hard to treat and has poor outcomes. Deeper understanding of the molecular underpinnings of mUC has identified potential biomarkers, biologic drivers, and relevant therapy targets. However, targeted therapies in mUC have had significant challenges due to molecular heterogeneity, clonal evolution, and genomic instability, and have not improved outcomes so far. Despite that, recent technological developments, clinical utilization of molecular biology, and discovery of new agents with preclinical and early clinical activity have signaled a new age of experimental therapeutics in mUC. The more frequent use of next-generation sequencing of tumor tissue and cell-free circulating tumor DNA, combined with novel agents tested in clinical trials, provides promise. There is a plethora of agents being tested in mUC, including inhibitors of receptors and signaling pathways (e.g., fibroblast growth factor receptor, human epidermal growth factor receptor, phosphatidylinositol 3-kinase/AKT/mTOR pathway), angiogenesis (e.g., vascular endothelial growth factor and its receptors), poly (ADP-ribose) polymerase (PARP) inhibitors, immuno-oncology agents, cytotoxic agents (e.g., chemotherapy, antibody drug conjugates), and epigenetic modulators, among others. Two agents, enfortumab-vedotin (antibody drug conjugate) and erdafitinib (fibroblast growth fac...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research