Research hotspots and frontier analysis of the novel immune checkpoint Nectin-4.

Abstract

Nectin-4 has emerged as a pivotal therapeutic target for antibody-drug conjugates (ADCs), particularly in advanced urothelial carcinoma (aUC) research. Although extensive literature has been reported on Nectin-4, it is worth noting that no studies have yet systematically investigated the hotspots, cutting-edge directions, and tissue expression of this target using a combination of bibliometric analysis and bioinformatics methods. Findings reveal growing interest in Nectin-4's role in cancer immunotherapy and ADC development. Urothelial carcinoma remains the primary focus, with breast and bladder cancers gaining traction. Key research priorities include optimizing ADC safety profiles, particularly managing cutaneous adverse events. Notably, dual targeting strategies combining Nectin-4 with TROP-2 show promise for next-generation ADC therapies. The study highlights evolving clinical needs, from target validation to treatment optimization, positioning Nectin-4 as a versatile biomarker bridging multiple cancer research domains. These insights emphasize the protein's translational potential while underscoring the importance of balancing therapeutic efficacy with toxicity management in ADC development.