Clinical Significance of Nectins in HCC and Other Solid Malignant Tumors: Implications for Prognosis and New Treatment Opportunities—A Systematic Review

SIMPLE SUMMARY: Nectins are attracting increased interest as potential markers for prognosis. In this review, we summarize the results of studies concerning the prognostic utility of the nectin family in different cancers. The reports on nectins-1-3 are ambiguous—both the upregulation and loss of expression could be a prognostic indicator. Nectin-4 is quite consistently overexpressed in tumors, which generally correlates with a worse prognosis. The data on nectins in hepatocellular carcinoma (HCC) are rather scarce and require further research. New treatments based on nectin-4 are currently being introduced, opening up possibilities for new lines of therapy. ABSTRACT: The nectin family comprises four proteins, nectin-1 to -4, which act as cell adhesion molecules. Nectins have various regulatory functions in the immune system and can be upregulated or decreased in different tumors. The literature research was conducted manually by the authors using the PubMed database by searching articles published before 2023 with the combination of several nectin-related keywords. A total of 43 studies were included in the main section of the review. Nectins-1–3 have different expressions in tumors. Both the loss of expression and overexpression could be negative prognostic factors. Nectin-4 is the best characterized and the most consistently overexpressed in various tumors, which generally correlates with a worse prognosis. New treatments based on targeting nectin-4 are currently being developed. Enfortumab vedotin is a potent antibody–drug conjugate approved for use in therapy against urothelial carcinoma. Few reports focus on hepatocellular carcinoma, which leaves room for further studies comparing the utility of nectins with commonly used markers.