Antibody-Drug Conjugates in Urothelial Carcinoma: A New Therapeutic Opportunity Moves from Bench to Bedside

Abstract

Significant progress has been achieved over the last decades in understanding the biology and mechanisms of tumor progression in urothelial carcinoma (UC). Although the therapeutic landscape has dramatically changed in recent years with the introduction of immune checkpoint inhibitors, advanced UC is still associated with rapidly progressing disease and poor survival. The increasing knowledge of the pathogenesis and molecular pathways underlying cancer development and progression is leading the introduction of target therapies, such as the recently approved FGFR inhibitor Erdafitinib, or the anti-nectin 4 antibody drug-conjugate Enfortumab vedotin. Antibody drug conjugates represent an innovative therapeutic approach that allows the combination of a tar get-specific monoclonal antibody covalently conjugated via a linker to a cytotoxic agent (payload). UC is a perfect candidate for this therapeutic approach since it is particularly enriched in antigen expression on its surface and each specific antigen can represent a potential therapeutic target. In this review we summarize the mechanism of action of ADCs, their applications in localized and metastatic UC, the main mechanisms of resistance, and future perspectives for their use in clinical practice.

Keywords

• urothelial carcinoma
• antibody-drug conjugates
• ADC
• Enfortumab vedotin
• ADC resistance mechanism