Sick dogs help test cancer drug at UI

Sick dogs help test cancer drug at UI

URBANA — Blaze didn't get a lot of years to wag her tail and chase squirrels. But before this 5-year-old golden retriever died, she may have helped take a bite out of cancer.

Blaze was one of the dogs helping test a cancer-busting drug called PAC-1, developed at the University of Illinois, that could be in human trials next year.

Research on this compound, which signals cancer cells to self-destruct, is being conducted on pet dogs with advanced cancer.

Blaze's owner, Phil Meyer of Springfield, said Blaze underwent a leg amputation for bone cancer — but wouldn't have lived long with her disease without those PAC-1 treatments at the UI.

"It gave us an extra year, year-and-a-half with our pet," Meyer said. "If we'd done nothing, she wouldn't have lasted a month. With the chemo and the PAC, it did a great deal of help for her, more than anything else."

PAC-1 was discovered in 2005 by UI chemistry Professor Paul Hergenrother, who has been testing and developing it ever since.

The drug has helped many of the dogs involved in the research, he said. Now he's preparing to find out if it will have the same effect on human cancer patients.

PAC-1 research was conducted on dogs with advanced blood cancers and advanced bone cancers that had spread to the lungs, according to Tim Fan, a veterinary medicine clinical professor who coordinated the PAC-1 canine trials at the UI Veterinary Teaching Hospital.

In people, the trial will be conducted on patients with brain cancer, a type of cancer with an extreme unmet need for new treatments, the researchers say.

Brain cancer is difficult to treat. The National Cancer Institute has projected 23,130 new cases of brain and nervous system cancers in the U.S. this year and 14,080 deaths from those cancers.

The current standard treatment for gioblastomas, the most aggressive form of primary brain tumors, extends survival but there is only so much treatment patients can tolerate, Hergenrother said.

PAC-1 targets a cellular enzyme called procaspase-3 found at elevated levels in many forms of cancers, including those of the breast, colon, liver, lung, skin, blood and brain.

"It gives cancer cells a signal to commit suicide," Hergenrother said.

Not only that, he said, but PAC-1 also spares the normal cells and can penetrate brain tumors.

One of the major obstacles in brain cancer treatments is that many major cancer drugs don't penetrate the brain, he and Fan said.

So how did man's best friend get involved in this research?

Dogs develop cancer naturally, just as people do. And because many of the biological mechanisms of cancer work the same way in people and dogs, that makes dogs a more accurate model of the disease in people than lab mice with the disease grown in their bodies, Fan said.

The research has been 100 percent voluntary for the dog owners, and they were well-informed of their therapy choices, he said.

"We were able to demonstrate that PAC-1, given orally, is well-tolerated in dogs with cancer," Fan said.

In some dogs, including Blaze, the tumors shrank in response to the therapy, he said.

For dogs with bone cancer, the dogs could also have conventional cancer therapies to see if there was additional benefit, and for most dogs, after they finished PAC-1, "there isn't a whole lot that was effective," Fan said.

Dogs with lymphomas that were switched to conventional therapy had their disease remain controlled, he said, but lymphoma is much easier to target.

Meyer recalls thinking PAC-1 was worth a try for Blaze, and he's glad to hear it's moving toward human trials.

His dog underwent eight PAC-1 treatments, the later ones at the family's expense, and throughout it all, Blaze was "a real trouper," he said.

Fan said Blaze eventually collapsed from heart failure known to be associated with the chemotherapy she was getting after her PAC-1 treatments.

PAC-1 dog research is continuing, not only in preparation for human trials but as treatment for dogs, Fan said.

Hergenrother said he's been contacted by a dog owner as far away as Michigan wanting to get a dog enrolled. A dog from Texas has already been involved, he said.

Dogs were initially given larger, less frequent doses, but Fan said new research will evaluate lower doses in dogs, administered by their owners every other day at home.

An investor who wishes to remain anonymous has given $2 million to help get the drug to human trials planned for the University of Illinois Cancer Center, Chicago.

Fan said plans are to start human trials by the third quarter of next year. But before that can happen, PAC-1 has to make it through a new drug review by the Food and Drug Administration.

Until he sees how the drug functions in people, Hergenrother said, he can't project what kind of impact it's going to have.

Fan said that for brain cancer patients, "any incremental improvement would be very meaningful."

If PAC-1 works in people, "it could be transformative," he added. "It could transform the landscape of how we could treat brain cancer in people."

Dogs with cancer won't be forgotten. The goal would be to develop two drugs in tandem, one for humans and another for canine cancer, Fan said.

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