Unknown Manufacturer
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: 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.
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: 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.
While ADH-1 has a single molecular target, N-cadherin, we believe its anti-cancer effect results from two distinct mechanisms of action - apoptosis and tumor vessel angiolysis. N-cadherin appears to act as a tumor cell survival factor. In cell culture studies, inhibition of N-cadherin binding between tumor cells has been shown to cause apoptosis of tumor cells, we believe as a result of disrupting the cadherin-regulated cell survival signals. ADH-1 also appears to disrupt the blood vessels needed for cancerous tumors to grow and flourish, with hemorrhaging having been noted in both our clinical and preclinical studies. We believe the mechanism for this disruption is either a competitive inhibition of the binding of cadherins between the endothelial cells of the tumor blood wall or apoptosis in tumor cells that form a part of the blood vessel wall, each leading to leakage and rupture of these vessels. The latter involves the phenomenon of tumor "mosaicism," in which tumor cells form a portion of the vascular wall (along with the endothelial cells). Induction of cell death of these tumor cells would result in tumor vascular disruption.
Investigated for use/treatment in breast cancer, cancer/tumors (unspecified), melanoma, ovarian cancer, and solid tumors.
One entry per invention. Patent families filed in the US, EP, WO and CN offices.
