As tumors become more aggressive, invasive, and malignant, contemporary cancer therapies have shown limited effectiveness. At this point in the life cycle of many tumors, researchers have found that N-cadherin is expressed in greater amounts, making it an important potential target for developing new anti-cancer treatments.
Early, well-differentiated cancers primarily express E-cadherin, like the epithelial cells from which they are derived. E-cadherin functions to establish and maintain the integrity of the tightly adhesive epithelial layer of cells. However, poorly differentiated, highly invasive cancers frequently lose their E-cadherin expression, and N-cadherin becomes over-expressed instead. This change in primary cadherin expression causes the epithelial cells to lose their tightly adhesive and well-defined shape and become loosely adhesive, flattened and migratory. Such “cadherin switching” promotes properties such as invasion and metastasis of the cancer, leading to a poor prognosis for the patient.
N-cadherin appears to be highly expressed in a wide variety of tumor types. In a comprehensive immunohistochemical analysis of N-cadherin expression in some 600 human tumor samples, Adherex found that 100% of liver and uterine cancers and squamous cell carcinomas of the skin, esophagus and larynx expressed N-cadherin. That study also found that 87% of kidney cancers, 83% of colorectal cancers and 60% of non-small cell lung cancers expressed N-cadherin. Thus, ADH-1 may have utility in a wide variety of cancers. Further, as tumors become more invasive and metastatic, the frequency of N-cadherin expression typically rises.
