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Southwestern, Canadian Researchers Collaborating on New Anti-Cancer Drugs

Frank Guziec, holder of the Dishman Chair in Science, and his wife, Lynn, an assistant professor of an assistant professor of chemistry, are collaborating with Brian Hasinoff, a professor of pharmacy at the University of Manitoba, on new drugs that would have the effectiveness of Doxorubicin without the toxicity.

Since the 1970s, a drug known as Doxorubicin has been one of the mainstays in treating solid tumors such as breast cancer, prostate cancer, ovarian cancer and lung cancer. Although effective in treating cancer, the drug has a dangerous side effect: Too much exposure can damage heart muscle.

“Doxorubicin is a very useful drug, but people can only take a certain amount of it in their lifetime,” says Frank Guziec, a professor of chemistry and holder of the Dishman Chair in Science at Southwestern. “Beyond that it becomes far too toxic.”

Guziec and his wife, Lynn, an assistant professor of chemistry, are collaborating with Brian Hasinoff, a professor of pharmacy at the University of Manitoba, on new drugs that would have the effectiveness of Doxorubicin without the toxicity.

Like many other anti-cancer drugs, Guziec explains, Doxorubicin works by binding to the DNA of cancer cells, which prevents the cancer cells from replicating. Unfortunately, the drug also interacts with other cells, particularly heart tissue.

While others have tried to modify Doxorubicin, the Guziecs have been able to synthesize new compounds with a totally different structure that will not react with heart tissue, but still retain their anti-tumor activity. These compounds, called anthrapyrazoles, are cyclic, flat molecules that can slide into the DNA structure in a process called intercalation, preventing cell growth.

The collaboration with Hasinoff began in the summer of 2004, when the two Southwestern professors spent the summer working in his lab in Winnipeg. They had already been developing similar compounds in their lab at Southwestern for about eight years.

The Southwestern researchers prepare the compounds and Hasinoff tests them on cell lines he grows in his lab. Hasinoff’s lab even has heart cells that can be used to test whether the compounds are damaging heart muscle.

“Neither of us could do this research alone,” Frank Guziec says. “This is the best kind of collaboration.”

The Southwestern researchers are working on developing about 12 different compounds. The process involved in synthesizing the compounds involves many steps and is very technically demanding. It takes about a month to make each compound.

Hasinoff uses “molecular modeling” to predict whether certain modifications to the structure of compounds will make them more effective.

The team has published two papers so far and has recently submitted a third for publication. Earlier this year, the researchers received a “provisional patent” on their work, which gives them a year to prove the principle behind their work.

Currently, the Guziecs are trying to develop a next generation of the compounds that will be more stable. “The compounds need to stay around in the body long enough to be effective,” Frank Guziec says.

If the researchers can develop more stable compounds, their goal is to partner with a pharmaceutical company that would have the resources to produce large quantities of the compounds and carry out further testing. The University of Manitoba’s Technology Transfer Office is seeking potential partners on the project, and recently listed the team’s work as its featured “Hot Technology.” (see http://www.hot-technologies.ca/newsletter/fall_2007/sept_2007.html)

If the concept can get fully patented, Guziec says, a company would have 20 years to bring it to market.

Several Southwestern students have been involved in the research project over the years. Jennifer Lang ’02 and Kimberly Lawson ’04 were involved in making the first generation of the compounds and Kyle Marshall, a senior chemistry major, is working on the next generation of compounds for his honors thesis in chemistry. Marshall presented a paper about how a new series of compounds were made at the August meeting of the American Chemical Society in Boston.