The Anti-Nectin 4: A Promising Tumor Cells Target. A Systematic Review

The Nectin cell adhesion protein 4 (Nectin-4) is overexpressed in multiple human malignancies. Such aberrant expression is corre-lated with cancer progression and poor prognostic. Nectin-4 has emerged as a potential biomarker and promising targeted therapy. This review aimed to gather the current state of the literature about Nectin-4 relevance in preclinical tumor models and to summarize its clinical relevance regarding cancer. A systematic assessment of literature articles was performed by searching in PUBMED (MED -LINE) from the database inception to May 2021, following PRISMA guidelines. Preclinical models unanimously demonstrated mem-brane and cytoplasmic location of the Nectin-4. Furthermore,Nectin-4 was overexpressed whatever the location of the solid tumors. Interestingly, a heterogeneity of Nectin-4 expression has been highlighted in bladder urothelial carcinoma. High serum Nectin-4 level was correlated with treatment efficiency and disease progression. Finally, generated anti-drug-conjugated targeting Nectin-4 induced cell death in multiple tumor cell lines. Nectin-4 emerges as a promising target for anticancer drugs development because of its central role in tumorigenesis, and lymphangiogenesis. Enfortumab vedotin targeting Nectin-4 demonstrated encouraging results and should be extended to other types of solid tumors.