OTTAWA, Ontario - Since blood vessels can constitute up to 10 percent of the volume of a solid tumor, a great deal of interest and research has been focused on anti-angiogenesis therapies designed to retard blood vessel growth, thereby inhibiting tumor formation.
Adherex Technologies Inc., an emerging biotech company in Ottawa, is working on a new approach to cancer therapy it believes has advantages over the anti-angiogenesis approach.
John Brooks, president & CEO of Adherex, told BioWorld International, the company licensed technology, discovered at McGill University in Montreal, that targets cell adhesion molecules. These molecules can be thought of as biological glues. They are important in maintaining the integrity of tissues by linking cells to other similar cells. The family of cell adhesion molecules known as the cadherins is responsible for this cell-to-cell adhesion.
It is known that cadherins bind to one another using specific amino acids in the molecule, called the cadherin cell adhesion recognition (CAR) sequence. The company has discovered and holds proprietary rights to small linear and cyclic peptides based on the cadherin CAR sequence that contain the amino acid sequence HAV (Histidine-Alanine-Valine). These small peptides will inhibit cadherin function by competing for the binding site on the cadherins. Adherex is the only company in the world that has patented synthetic compounds capable of altering cadherin function in this way, Brooks said.
Releasing data from animal studies, the company's collaborating scientists at McGill University, Georgetown University in Washington and the Weizmann Institute in Israel, have successfully stopped breast and ovarian tumor growth in mice using a new compound known as Exherin.
A tumor is dependent on its blood vessels for oxygen and other nutrients. These tumor blood vessels are malformed compared to normal blood vessels. The malformation includes weaker adhesion between cells, which allows Exherin to disrupt the adhesions without affecting normal blood vessels. In preliminary safety tests, no apparent side effects were observed in healthy mice treated with up to 50 times the therapeutic dose, Brooks said.
The new approach targets the adhesion system that blood vessel cells use to connect to each other. The cells literally become "unglued." Treatment of tumors with Exherin results in breaking apart the blood vessels that feed the tumor. Exherin acts on both pre-existing tumor blood vessels as well as new vessels being formed and appears to work extremely quickly - within 24-hours, the researchers discovered.
"We are cautiously optimistic about our animal experiment data," said Orest Blaschuk, an associate professor at McGill University and chief scientist of Adherex. "While this research is in the early stages, Exherin's consistent and efficient ability to stop human breast and ovarian tumor growth in mice is very impressive."
The significance from the results, Brooks said, is demonstration that it is possible to destroy tumor blood vessels, and if a safe an efficacious drug can be developed in the future, the anti-adhesive approach to cancer therapy will be faster and may not require treatment over a long period of time.
In the months ahead further work will be done in order to prepare for an investigational new drug application. The company expects clinical trials to begin by the end of 2000.