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

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.

Prognostic Potential of Nectin Expressions in Colorectal Cancer: An Exploratory Study

“…Although it is weakly expressed or nearly absent in healthy adult tissues, nectin-4 plays a crucial role during embryonic development, contributing to organogenesis [29,38,51]. Numerous reports indicate that nectin-4 is overexpressed in a wide array of cancers such as colorectal, gastric, esophageal, breast, ovarian, hepatocellular, non-small-cell lung, urothelial, papillary thyroid, and renal cancers [14,25,27,29,52]. This overexpression suggests that it may serve as a potential biomarker or therapeutic target in the treatment of these malignancies.…”

“…Through these interactions, nectins participate in various biological processes, including immune responses, cell growth, and migration [12,13]. According to the available scientific literature, cancer diseases may be accompanied by significant variability in nectin expression on the surface of tumor cells [14]. The significance of this variability and potential clinical use in CRC has not yet been well researched.…”