College of LAS « Illinois

Chemical Sciences

Top Dog

Chemists, vets, and dogs work together for cancer cure.

researchers

When Kim Kliethermes noticed their dog, Hank, limping just before Christmas of 2012, she thought he had reinjured his right rear leg. After all, Hank had ruptured a ligament in the same leg three years earlier and had it repaired at the University of Illinois Veterinary Teaching Hospital. But when her local veterinarian in the Peoria area X-rayed the leg, he saw a shadow in the bone.

Hank, a 10-year-old black Labrador, had osteosarcoma—bone cancer.

The local vet immediately referred Kim and Craig Kliethermes back to the U of I, and over the past year their dog Hank has become more than man’s best friend; he has become humanity’s best friend by becoming part of two important drug trials. One of the trials is testing a promising new drug—discovered at Illinois—that could potentially help thousands of people suffering from cancer.

The drug, PAC-1, was discovered in the mid-2000s in the lab run by Paul Hergenrother, an LAS professor of chemistry. Not long after he discovered PAC-1, Hergenrother began a unique collaboration with Timothy Fan, a U of I veterinary oncologist. They began using PAC-1 with dogs that had already developed cancer and had no options left—dogs such as Hank. Illinois researchers have also been conducting tests in a collaborative study at Johns Hopkins University, and the results have been dramatic.

“My students have found that PAC-1 has a tremendous ability to synergize with other cancer drugs,” Hergenrother says. “That is what really got us excited about this compound.”

Another major benefit is that PAC-1 can penetrate the “blood-brain barrier” to reach brain tumors—a rare quality. Currently, the only approved drug that can get to tumors in the brain is Temozolomide, or TMZ, but if testing continues to go well, PAC-1 is poised to become the second.

With such successes in the initial trials, human trials with PAC-1 are scheduled to begin in the summer of 2014. The potential of PAC-1 also led Hergenrother and Fan to team together to establish a Champaign-based company, Vanquish Oncology, to develop the drug. In addition, an anonymous investor has contributed $2 million to move the drug into human trials.

But how does PAC-1 work?

Normally, our body is programmed to kill off cancerous cells, but as Hergenrother notes, “Some cancers are notorious for their ability to evade the cell death process.” PAC-1 confronts this problem head-on by activating cell death, or apoptosis, in cancer cells.

“It kills cancer cells fairly potently, but not adjacent normal tissue,” he says. When Carle Hospital in Champaign supplied his lab with colon cancer tissue and healthy adjacent tissue, Hergenrother confirmed that PAC-1 goes after the cancer cells with a vengeance, but spares the healthy “margin tissue.”

Veterinary oncologist Fan says that in his collaboration with Hergenrother, they have so far used PAC-1 on about 20 dogs that had developed cancer. In 2010, they published the results with the first six dogs, and four of the animals showed a positive clinical effect—either stabilizing or shrinking the tumors.

dogs

According to Kim Kliethermes, when Hank was first diagnosed with bone cancer a year ago, U of I vets added him to a trial with Zometa—a drug that increases bone density. After that, Hank’s limp disappeared, he was not in any observable pain, and he beat the odds, for he was expected to live only about two to six months. However, about nine months after the diagnosis, Illinois vets found that he had a small mass in his lung; and when they retested one month later, they found that the mass was growing. Cancer had entered his lungs.

“I was sobbing uncontrollably when the doctor gave me the news, and he teared up as well,” Kliethermes says. “For him to be that compassionate, it meant the world to me.”

After the Kliethermes family received the bad news, they enrolled Hank in a second drug trial—an eight-week U of I trial with PAC-1. However, when Hank first began the PAC-1 trial, he experienced some chemotherapy-related side effects, including vomiting and loss of appetite for an entire weekend, Kliethermes says. Illinois veterinarians theorized that his therapy-associated toxicity meant that PAC-1 was making chemotherapy more potent—the synergistic effect in action. Because PAC-1 had increased the treatment potency, they scaled back the dosage of his chemotherapy.

Other than that first weekend of discomfort, Kliethermes says the good news is that Hank has remained his usual happy-go-lucky self.

“Labradors have such winning personalities,” she says. “Hank loves other animals. He loves people. He loves everybody. Our world is going to be a lot grayer when we lose him.”

But as hard as it is, they also see the contribution their dog is making.

“We want to contribute to the science in any way we can, as long as it doesn’t reduce the quality of life for my dog to the point that it’s not worth it,” she says. Their family chose to help because they have seen the ravages of cancer firsthand; Craig’s mother died from breast cancer about a year and half ago.

“If my dog somehow contributes to an effective treatment method for humans down the road, imagine what a legacy that would be,” Kim Kliethermes says. “It’s exciting that Hank gets to be a part of that.”

By Doug Peterson
Winter 2014