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Boosting Hope in the Fight Against Pancreatic Cancer

May 9, 2010

Pancreatic cancer was pushed to the forefront of the news last year when actor Patrick Swayze died from it. More than 35,000 other people in the United States also died from pancreatic cancer in 2009.

Pancreatic cancer is one of the most deadly cancers. Because the pancreas is tucked behind the stomach deep inside the body, routine physical exams rarely find early pancreatic tumors. In addition, patients often don’t have symptoms until the cancer has spread to other organs. As a result, fewer than 5 percent of people survive pancreatic cancer beyond five years.

Pancreatic cancer cells are also known to be particularly stealthy and spread early in the disease stage.

“In other cancers, tumors usually have to be large before cancer cells spread to the lymph nodes and other organs,” explains William Hawkins, MD, a Washington University gastrointestinal surgeon at Barnes-Jewish Hospital and the Siteman Cancer Center who specializes in this disease. “But with pancreatic cancer, even a 1-centimeter cancer can spread to the lymph nodes. Its tendency to spread quickly undetected is one reason why pancreatic cancer is so deadly.”

In the rare 15 percent of cases where pancreatic cancer hasn’t spread to other organs, patients may be candidates for surgery to remove the tumor. For this group, the survival rate increases to 20 percent.

Heeding the Call for Better Treatment Options

The National Cancer Institute has designated development of an effective treatment for pancreatic cancer one of its highest priorities. Thanks to research on immunotherapy being done by researchers like Dr. Hawkins, better treatment options are on the horizon.

The first step to better treatments has been identifying pancreatic tumors by a readily detectable marker that shows promise as a basis for immune therapy against the cancer. The marker is mesothelin, a protein that may play an essential role in the development and growth of cancer. This makes it an ideal target for immune therapy.

Researchers found that immune cells taken from pancreatic cancer patients can be coaxed to target mesothelin.

“If we can turn on the immune system to attack cells that have mesothelin, that might become an important part of pancreatic cancer therapy,” says Dr. Hawkins, a principal investigator and co-author of a study on this topic recently published in Clinical Cancer Research. “Because mesothelin in pancreatic cells spurs tumor growth, loss of mesothelin could make cancer cells behave more like normal cells. That means even if immunotherapy only knocked out the mesothelin in pancreatic cancer cells instead of killing the cells, it could still be effective.”

Triggering an Internal War Against Cancer

One way to activate mesothelin-specific immune cells is through a vaccine, which would boost the immune response to mesothelin to target pancreatic cancer cells.

Dr. Hawkins is conducting a clinical study of an agent that may activate specific immune cells in pancreatic cancer patients. Additional research, funded by the Barnes-Jewish Hospital Foundation, includes testing vaccines that train the immune system to create antibodies to attack cancer cells, and testing methodologies to reduce cancer’s ability to suppress immune responses.

Dr. Hawkins says the next generation of treatment will combine immune stimulation with a vaccine. “We believe the best therapy is a three-pronged immunotherapy approach,” he says. “We’re building toward that now.”

David Linehan, MD, a Washington University gastrointestinal surgeon and researcher, is also focusing on research to impede cancer’s ability to turn down immune response, which prevents the immune system from attacking cancer cells.

“Our goal is to stimulate the immune system so it recognizes cancer cells as dangerous and gets revved up against them,” Dr. Hawkins says. “We hope to trigger the immune system to target the mesothelin in pancreatic cancer cells. The question is how do we present the molecule so the immune system is angry about it and mounts an immune response against it, but not against healthy cells?”

The immune system is a powerful weapon that can turn for or against the body, he explains. “In autoimmune diseases, the immune system can kill a kilogram of normal healthy tissue while leaving the rest intact. We must find the switch that will get the immune system to look at a cancer and attack it. This will open a new cadre of treatment that is less toxic and more effective.”

Putting the Puzzle Together

Dr. Hawkins notes pancreatic cancer researchers are using information from the Human Genome Project, mapped at the Washington University Genome Center, and are working with researchers on other cancers. “The goal is to translate this immunotherapy approach to other cancers, too, including breast cancer. There is such a big effort on many fronts. It’s a huge jigsaw puzzle, and it will take time to put it all together.”

Dr. Hawkins is very optimistic about the future of pancreatic cancer treatment. “Five years ago, we didn’t have anything to treat this disease. But recently we’ve begun to accelerate progress, and we’ve seen our first increase in survival rates in 50 years. There’s more hope now than ever before.”

Gifts to the Foundation Bring a Life-Giving Return on Investment

Dr. Hawkins credits the Barnes-Jewish Hospital Foundation with helping researchers get to this point. “The Foundation is almost like a venture capitalist. Five years ago, I was a young guy with ideas who wanted to make a difference. The Foundation bet on my ideas and gave me the resources to get started with research. As a return on investment, I’ve hired five people in our lab and generated more than $2 million more in research funding to attack pancreatic cancer. The Foundation’s investment has paid off.”

Despite the progress made in pancreatic cancer treatment, Dr. Hawkins says this is just the tip of the iceberg. “I still have a lot of work to do — we’ve got some cancers to cure. I see this not as a 5K but rather a marathon. Donors’ gifts mean so much because they offer hope through research and new treatments to patients in St. Louis and beyond.”

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