Nectins and Nectin-like Molecules in Colorectal Cancer: Role in Diagnostics, Prognostic Values, and Emerging Treatment Options: A Literature Review

Abstract

In 2020, colorectal cancer was the third most common type of cancer worldwide with a clearly visible increase in the number of cases each year. With relatively high mortality rates and an uncertain prognosis, colorectal cancer is a serious health problem. There is an urgent need to investigate its specific mechanism of carcinogenesis and progression in order to develop new strategies of action against this cancer. Nectins and Nectin-like molecules are cell adhesion molecules that take part in a plethora of essential processes in healthy tissues as well as mediating substantial actions for tumor initiation and evolution. Our understanding of their role and a viable application of this in anti-cancer therapy has rapidly improved in recent years. This review summarizes the current data on the role nectins and Nectin-like molecules play in colorectal cancer.

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

“…Nectin-3 is present in healthy, mature human tissues, including the gastrointestinal tract. It is found on the surface of T lymphocytes and plays a role in the organogenesis of organs such as the eye and cerebral cortex [12,23,25,38].…”

“…Nectin-4 is another member of the nectin family that has significant implications both in physiology and in various diseases. 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].…”

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

“…Apart from homo-and heterophilic interactions within the nectin family, there are other functions that nectins exhibit by binding specific proteins-especially immune modulation, cell survival, growth and proliferation signaling, and viral entry. Among others, the physiological functions of nectins include angiogenesis, leukocyte vascular migration and other cells' migration [9,[11][12][13] Members of the nectins and necl families have a regulatory function in T-lymphocytes and natural killer (NK) cells. Studies in recent years have shed light on nectins' and necl's interactions with T-cell immunoglobulin and ITIM domain (TIGIT) family receptors, which determine the activity of immune cells.…”

“…This characteristic was the basis for further studies on this nectin's utility in determining the diagnosis, prognosis and possible treatment targets for cancer. Currently, Enfortumab vedotin-a monoclonal antibody-drug conjugate targeting nectin-4-is used as another tool for treatment of urothelial carcinoma [12,17,18]. The characteristics of the nectin family have been summarized below (Table 1).…”