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New vaccine may help treat pancreatic cancer The second of two parts / Sunday: Jai Pausch on Learning to live after the 'Last Lecture'

Monday, July 27, 2009 By Mark Roth, Pittsburgh Post-Gazette

 

Everyone calls the Rev. Clifford Stollings (Pictured here on the right) a miracle.

He is not really comfortable with that description, but he's willing to admit he is a rarity -- a pancreatic cancer patient who has survived for six years.

Pancreatic cancer remains the most lethal of all the major cancers, with a five-year survival rate of only 5 percent. Many patients die within two to three months of their diagnosis.

Randy Pausch, the Carnegie Mellon University computer science professor who died a year ago Saturday, was considered an exception because he managed to live almost two years past his diagnosis.

So Mr. Stollings, an 83-year-old retired Methodist minister living in Uniontown, knows how lucky he is to be cancer-free so long after his 2003 diagnosis.

"It's sort of unimaginable in a way," he said last week. "Everybody wants to tell me that I'm a miracle, but I don't know quite what to do with that description theologically.

"People often think of a miracle as someone God has picked out for some special mission in the world, and I don't have any sense that it was more important for me to live for six years as opposed to some other minister who was just as good a person or preacher."

But his survival, he said, "is certainly a great grace from God."

It may also be attributable to an experimental vaccine developed by UPMC researcher Olivera Finn that he took as part of his treatment.

The vaccine is aimed at a protein that pancreatic tumors overproduce, and it has shown some effectiveness in preventing recurrence in people who already have had cancer surgery, like Mr. Stollings.

This fall, Dr. Finn and her colleague, Dr. Randall Brand, hope to use the vaccine on patients before they get surgery. If that experiment shows the vaccine has helped reduce the number of cancer cells in the excised tissue, they will launch a trial to see if the vaccine can prevent the need for surgery in the first place, she said.

The first approach in pancreatic cancer now is usually surgery, and that poses its own problems. Because the pancreas, which sits below the stomach in the middle of the torso, is responsible for secreting insulin and certain digestive enzymes, removing it can cause instant diabetes and require patients to take insulin, as well as special enzymes to digest their food.

That provides extra motivation to researchers to find ways to prevent pancreatic cancer or treat it before it requires extensive surgery.

Vaccines are just one new method for treating pancreatic cancer that have researchers and disease activists more excited than they have been in years.

Julie Fleshman, president and CEO of the Pancreatic Cancer Action Network, said there finally seems to be strong momentum building to tackle this deadliest of all malignancies.

At a time when many other types of cancer got less federal research funding, the National Cancer Institute raised allocations for pancreatic cancer by $14 million this year, for a 20 percent increase.

At a time when many other types of cancer research got less federal funding, the National Cancer Institute -- which oversees federal spending for cancer research -- raised allocations for pancreatic cancer by $14 million this year, a 20 percent increase.

In addition, Stand Up To Cancer, a private fund-raising effort for cancer research led by CBS newswoman Katie Couric and several women executives in Hollywood, raised about $100 million in pledges last year, and the largest single grant was given to pancreatic cancer research, Ms. Fleshman said.

She attributed much of the trend to Dr. Pausch, who not only inspired people with his last lecture on how to live a meaningful life but became a forceful advocate for pancreatic cancer research before his death.

"He brought the whole effort up to a different level than we had been able to do prior to him being involved," she said.

The new research on pancreatic cancer focuses on three goals: identifying people at higher risk of getting the cancer, detecting precancerous tissue changes earlier, and then giving people targeted biological therapy with fewer harsh side effects than traditional radiation and chemotherapy.

Providing earlier treatment for this cancer is especially important because it is so insidious, said UPMC's Dr. Brand.

"The problem with the pancreas is that it's in a god-awful location," he said, Doctors can't feel the tumor and have to examine it indirectly with imaging tests. "But, it spreads early and yet it doesn't develop symptoms until late."

Because pancreatic cancer strikes just 1 percent of the population, finding people at higher risk of it is a key goal, he and others said.

Researchers are starting with people who have a family history of the disease.

By tracking these people and analyzing their DNA, they are hoping to find biomarkers that not only predict who is most likely to get the disease, but also provide potential new targets for treatment.

Their work is being accelerated by the increasing sophistication and plummeting cost of genetic sequencing, said Dr. Anirban Maitra, a scientist at the Johns Hopkins Medical Institutions.

"We can now get sequencing of a person's entire genome for about $10,000," he said, "and I believe that could drop to a couple thousand dollars in a few years, which when you think about it is about what it costs for an expensive diagnostic test today."

Using that technique, a group led by Dr. Alison Klein at Johns Hopkins this year became the first in the world to sequence all 20,661 protein-coding genes in a person with familial pancreatic cancer. By comparing them with normal genes, they were able to identify a new gene that probably caused the patient's cancer -- and could be a target of future therapies.

For those who sometimes question the value of basic research, she noted that "this new approach we used would never have been possible without the Human Genome Project," the 13-year, $3.3-billion public-private venture that developed the first techniques for rapidly identifying a person's DNA.

On the treatment side, a tool that is becoming increasingly important is ultrasonic endoscopy. Doctors put a tube down the patient's throat into the stomach, and a water-filled tip at the end bounces sound waves off the pancreas, showing whether there are cysts or other precancerous lesions. The device can even withdraw pancreatic cells for analysis.

Eventually, doctors may be able to genetically profile those biopsy specimens to see whether a particular therapy would work best on the person's tumor.

Besides vaccines, which are designed to boost a person's immune system to fight cancer, researchers also are developing other therapies to block particular aspects of the tumor's growth.

Johns Hopkins' Dr. Maitra is working on one based on a gene that normally makes proteins involved in DNA repair but seems to be hyperactive in pancreatic cancer, he said.

Early human trials are under way on four drugs that appear to block the action of the gene. In animal studies, scientists have found that these agents "basically make the cancer cells go cold turkey and they crash and burn much faster than a normal cell would."

And they don't seem to have the toxic effects of normal chemotherapy, he added.

Despite these promising signs, researchers still have a long way to go, Dr. Brand noted.

He's searching for biomarkers that can give early warning of pancreatic cancer, but "there are no biomarkers today that are 100 percent accurate."

In the short run, he said, scientists may have to develop a whole set of biomarkers that reflect partial risks for the disease, and that may allow early treatments that could result in 40 percent of patients surviving for five years instead of today's dismal 5 percent.

"It's an intermediate step, but it's a realistic step. Sometimes you have to be practical. Not everybody can shoot for the holy grail."

Dr. Herbert Zeh and Dr. James Moser, two leading pancreatic cancer surgeons at UPMC, said there are also new surgical techniques that may improve survival.

The most challenging operation being used now is the Whipple procedure, which takes out the right half of the pancreas and then reconnects the remaining portion to the stomach and gall bladder.

The two surgeons have now done about 20 Whipple procedures using seven tiny incisions and a robotic device called the da Vinci Surgical System. It allows them to see a 3D image inside the body, and rotate the surgical instruments for precise suturing in a way they never could do using their own hands.

Ultimately, they would like to detect tissue changes early enough that they could take out just small parts of the pancreas and avoid the risk of the patient becoming an insulin-dependent diabetic.

That's what happened to Mr. Stollings, who now must inject himself twice a day with insulin and take an expensive enzyme to help digest his food.

The tradeoff is more than worth it, he said.

"To be frank" he said, "I pretty much gave myself up for death before surgery." I was 78 at the time, and because of all the material I had read, I didn't give myself much of a chance.

"My wife and I have been grateful for this time and the opportunities it's given us."

And despite the uphill climb that remains in research, diagnosis and treatment, Dr. Zeh said he firmly believes "there will be a tomorrow without pancreas cancer."

"It may not happen as quickly as we'd like it, but I believe we will get there someday."