Mouse experiment leads to rare cure of pancreatic cancer

A Spanish physician at the National Cancer Research Center (CNIO) is investigating whether laboratory mice can be employed in successfully treating patients with pancreatic cancer - a disease that is almost always fatal once it is detected.

Dr Manuel Hidalgo, who until recently was on staff at Johns Hopkins in Baltimore, believes lab rodents were the key in helping what he described as "the first cure of advanced pancreatic cancer."

The method used - which until now has only been applied to one single patient - is a combination of genetic analysis to determine which drugs work best and experimentation directly on the tumor itself. "We got lucky and guessed right because there was no margin for error," Hidalgo said.

"I had weeks to live, but now I am alive four years later"

The mice played an important role. The patient's tumor had been transplanted into the mice so doctors could experiment with different treatments to determine which worked best without having to expose patients to costly and painful drugs with severe side effects.

The clinical volunteer was Mark Gregoire, who is now 65. "He arrived at the hospital in a wheelchair. He looked more like a candidate for palliative care rather than one who was likely to be cured," says Hidalgo.

In May 2006, Gregoire was given just weeks to live. He was 61 years old, with aggressive pancreatic cancer and little hope of survival. Married with two daughters and three grandchildren, Gregoire ran a bicycle repair business in Florida. His brother suffered from the same disease and his sister had died of it at age 40.

Mark was not happy with the attention he was getting at the Miami Medical Center so he decided to contact Johns Hopkins in Baltimore, where his brother had been treated and had been quite happy with the doctors there.

Typically, Gregoire would have suffered the same fate as his siblings. Pancreatic cancer carries the worst prognosis of all types of the disease: 95 percent of patients die, said Hidalgo.

In a telephone interview, Gregoire explained that he contacted a staffer at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins one day in June 2006. The following week, he was speaking to Dr Hidalgo by phone about the clinical trial that was taking place at Johns Hopkins. A few days later, Gregoire was in surgery in Baltimore to remove parts of his tumor for the experiment.

The mice that were now carrying Gregoire's tumor were subjected to different treatments, twice weekly for four weeks. The most effective turned out to be mitomycin C, a drug that prevents the proliferation of tumor cells by building bridges in the double helix of DNA.

Meanwhile, Gregoire was being treated with gemcitabine and chemotherapy, which had proved ineffective. The disease had begun to take its toll on him. The physicians decided to treat him with mitomycin C, being the most effective remedy tried on the mice.

For four months the drug was administered, causing the tumor markers in his blood to decrease by 50 percent per month until the pancreatic tumor totally disappeared. Meanwhile, because of side effects, he had to be given painkillers for 12 months. "The doctors always informed me in detail about the process," he explains. "I knew it was experimental and, like everything else in this field, had its risks. But the first doctors I had seen had given me weeks so I had nothing to lose.

"And look, I'm still here now, four years later. I know very well about pancreatic cancer, because of my siblings. In total, three of the seven members of my family had it. Doctors didn't have to tell me how deadly it was to convince me; it was a privilege to undergo this treatment. Without it, I would be dead today."

The work has been published in the journal Molecular Cancer Cell.

Nearly two years after his surgery, Gregoire's cancer has spread to his lung and he is undergoing further treatment.

"But I feel very good, excellent," he says. "So much better than four years ago, of course. Back then I was given weeks to live. Today I can lead a normal life. The cancer is far less threatening and I am getting treatment for it. It is nowhere near as aggressive as the pancreatic cancer was."