Elucidation of Novel Molecular Targets for Therapeutic Strategies in Urothelial Carcinoma: A Literature Review

Abstract

Urothelial carcinoma therapy is a rapidly evolving and expanding field. Traditional cytotoxic chemotherapy regimens have not produced optimal long-term outcomes, and many urothelial cancer patients have comorbidities that disqualify them as chemotherapy candidates. In recent years, a plethora of novel therapeutic agents that target diverse molecular pathways has emerged as alternative treatment modalities for not only metastatic urothelial carcinoma, but also for muscle-invasive bladder cancer and non-muscle invasive bladder cancer in adjuvant and definitive settings. This review paper aims to discuss the various categories of therapeutic agents for these different types of urothelial cancer, discussing immunotherapy, antibody-drug conjugates, kinase inhibitors, CAR-T cell therapy, peptide vaccination, and other drugs targeting pathways such as angiogenesis, DNA synthesis, mTOR/PI3K/AKT, and EGFR/HER-2.

Keywords: FDA approvals; bladder cancer; clinical trials; molecular targets; targeted therapy; urothelial carcinoma.

Figure 1

Mechanisms of action for the FDA-approved treatments for advanced/metastatic urothelial carcinoma. There are currently 6 FDA-approved agents for the treatment of MIBC, which work through diverse mechanisms, including checkpoint inhibition and blockage of the FGFR signaling pathway (16). The therapeutic agents are marked by asterisks and are in bolded boxes.