Beyond conventional chemotherapy: Emerging molecular targeted and immunotherapy strategies in urothelial carcinoma

- Conventional chemotherapy for urothelial carcinoma has reached the plateau.
- No molecular targeted therapy is available in urothelial carcinoma.
- Molecular profiling revealed actionable genetic alterations, such as PIK3CA, FGFR3, and HER2.
- Immune checkpoint inhibitors demonstrated early promising results.
- Novel clinical trials incorporating molecular and immune biomarkers are warranted.

Advanced urothelial carcinoma is frequently lethal, and improvements in cytotoxic chemotherapy have plateaued. Recent technological advances allows for a comprehensive analysis of genomic alterations in a timely manner. The Cancer Genome Atlas (TCGA) study revealed that there are numerous genomic aberrations in muscle-invasive urothelial carcinoma, such as TP53, ARID1A, PIK3CA, ERCC2, FGFR3, and HER2. Molecular targeted therapies against similar genetic alterations are currently available for other malignancies, but their efficacy in urothelial carcinoma has not been established. This review describes the genomic landscape of malignant urothelial carcinomas, with an emphasis on the potential to prosecute these tumours by deploying novel targeted agents and immunotherapy in appropriately selected patient populations.