UPMC's Liver Cancer Center hopes a clinical trial it is conducting will showcase the benefits of viral gene therapy in treating colorectal cancer that has spread to the liver.

University of Pittsburgh Medical Center's liver cancer center is participating in a national trial to test whether a genetically engineered herpes simplex virus -- the one that causes cold sores -- will kill liver cancer without harming healthy tissue.

Dr. David A. Geller, co-director of the liver cancer center and principal investigator at the UPMC site, said the center is approved to use the virus therapy on five patients in the trial.

Already therapy has begun on one patient, with four other slots yet to be filled. A second candidate is under consideration, he said.

MediGene AG, the German company sponsoring the study through its San Diego subsidiary, genetically "disarmed" the herpes simplex virus so it can serve as a therapeutic agent in humans.

It accomplished that goal by switching off a gene that normally enables the virus to multiply and kill healthy cells. The new version thrives only inside cancer cells whose environment compensates for the lost gene. As a result, the virus replicates inside tumor cells and destroys them without effect to healthy cells.

"In animal cells and human tumor cell lines, the virus was a cancer killer," said Dr. Geller, describing participating patients as "pioneers in cutting-edge medicine."

The trial will determine whether the virus kills colorectal cancer that has metastasized to the liver. Dr. Geller said 150,000 new cases of colorectal cancer are diagnosed each year, and 60 percent of those cases metastasize to the liver over the lifetime of the patient.

It's the same cancer that has stricken presidential spokesman Tony Snow, 51. Mr. Snow, who had his colon removed in 2005 due to colorectal cancer, was told last week that the cancer has spread to his liver.

To qualify for the UPMC study, participants must have inoperable metastatic colorectal cancer to the liver and have failed first-line chemotherapy.

Viral gene therapy is designed to improve the response to second-line chemotherapy, whose current success rate is only 15 to 20 percent.

The one participant, whom Dr. Geller could not identify without the man's permission, has 12 spots scattered in his liver, making it inoperable.

During the trial, the subject will receive four doses of the genetically engineered herpes virus every Monday for four weeks. Doses are injected into a catheter inserted into the liver's hepatic artery during a two-hour procedure. The study will track the virus to see if it ventures beyond the liver.

Normal herpes simplex viruses can migrate to the brain and cause encephalitis. To prevent that, participants must show the presence of antibodies to fight off any wayward virus that escapes the liver. To date, the modified virus appears to be safe with no documented herpes infections in participating patients.

"You have to show immunity and prior exposure to the herpes virus so it can ward off the virus if it escapes," Dr. Geller said.

Even if the virus escapes the liver, the patient can be treated with Acyclovir, an antiviral medication used for cold sores.

Eighteen patients nationwide will be treated at four hospitals, including UPMC, in Phase II of the study. Eight of those spots already have been filled. During Phase I, 12 patients proved the novel therapy was safe.

"Preliminary results were encouraging," Dr. Geller said. "But it will be a year or two before we know the outcome of this study."

Studies on animals, including monkeys, have shown that the genetically engineered virus is safe and kills cancer. But in human clinical trials, procedures must be conducted under tighter scrutiny.

"I think this is the good fight," Dr. Geller said, noting two years of paperwork to land approval to conduct the trial at UPMC.

Educating people about liver cancer also is important, he said. Even if people don't qualify to participate in the trial, other treatments are available. More information is available at www.livercancercenter.upmc.com or by calling 412-692-2001.

In 2006, 1,728 liver cancer patients were seen at UPMC, including 350 new cases. At the center, one of the largest in the United States, 95 percent of patients qualify for some form of cancer therapy.

"The best option is to surgically remove the cancer," Dr. Geller said.

About a third of those patients are cured. Although the study focuses on inoperable metastasized colorectal cancer, the eventual goal, if the study succeeds, would be to test it on other types of liver cancer, which is difficult to cure.

About 25 percent of UPMC liver cancer patients survive three years after diagnosis. The most aggressive form of the disease is primary liver cancer -- hepatocellular carcinoma or HCC -- for which there is no effective chemotherapy.

"The data is humbling," Dr. Geller said. The best treatment for HCC is a liver transplant. "If we can detect it early, we can cure it by surgically removing the tumor. There's a 30 percent cure rate if we catch it early."

Unfortunately, he said, about 75 percent of liver cancer is inoperable at time of diagnosis.

Primary liver cancer can result from cirrhosis of the liver, hepatitis B and C infections, chemical exposure, or autoimmune liver disease. Fifteen percent of HCC victims had no risk factors.

He said the viral gene therapy could be the dawn of a new era in liver cancer treatment.

"It has the potential to significantly improve the treatment responses when combined with traditional chemotherapy," Dr. Geller said.