Description |
Adherex's biotechnology compound, ADH-1, targets N-cadherin, a protein present on certain tumor cells and established tumor blood vessels. ADH-1 is currently in clinical development in a combination program with a range of chemotherapeutic agents to investigate the synergistic effects noted in our preclinical models. At the end of 2006, the Company also completed patient enrollment in our single-agent Phase Ib/II and Phase II trials of ADH-1.
Cadherins are cell adhesion and cell signaling molecules crucial to the development of tissues, organs and organisms. Agents that target and inhibit cadherin function have the potential to attack the progression of cancer at two distinct points:
* Direct targeting of cadherins expressed on cancer cells may disturb cadherin-mediated signaling, leading to apoptosis (death) of cancer cells.
* Cadherin inhibitors may exploit the inherent structural weaknesses of the tumor vasculature, causing angiolysis (disruption of blood vessels) and tumor damage.
As many tumors become more aggressive, invasive, and malignant, researchers have found that N-cadherin is expressed in greater amounts, making it an important target for developing anti-cancer treatments.
Poorly differentiated, highly invasive carcinomas are characterized by over-expression of N-cadherin (as opposed to E-cadherin). This change in primary cadherin expression causes the epithelial cells to lose their tightly adherent, polarized and well-defined shape and become loosely adherent, flattened and migratory. Such cadherin switching promotes properties such as dedifferentiation, local invasion and metastasis, leading to poor prognosis.
ADH-1 may have utility in a wide variety of cancers as N-cadherin is overexpressed in a variety of tumors. As tumors progress to become higher grade, invasive and more metastatic, the frequency of N-cadherin expression generally rises.
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