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Can Pancreatic Cancer Be Stopped?

November 29, 2011 By:
Elyse Glickman | JE Feature
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The death of Steve Jobs from pancreatic cancer two months ago resonates as a story of American triumph overcome by tragedy.

During the same month that Jobs died, Ralph Steinman, 2011 Nobel Prize Laureate for Medicine, passed away from the same disease just days before the Nobel Foundation announced his win for the discovery of the dendritic cell and its role in adaptive immunity.

A frighteningly high 90 percent of patients reportedly die within the first year of diagnosis of pancreatic cancer, but the high-profile deaths of these two men underscore the urgency of finding treatments and cures.

Though many recent attempts to curb and cure the disease have not staved off the fourth deadliest form of cancer in the United States, several physicians and institutions in Philadelphia are endeavoring to change this.

"The loss of these talented gentlemen is a reminder that there are still many cancers for which we don't have a cure," stresses Dr. Chi Van Dang, director of the pancreatic cancer "Dream Team" at the Abramson Cancer Center at the University of Pennsylvania and longtime member of the American Cancer Society's Stand Up to Cancer.

"With a number of expert surgeons and great research medical institutions in the Philadelphia area," the doctor adds, "the city is sparked by the desire to eradicate this deadly disease."

The Abramson Cancer Center is in the forefront of research for the way its physicians and researchers have taken a "superhero approach" -- acting agressively in educating patients -- in the fight against this cancer. Van Dang notes that an approach to curbing the illness' reign of terror is to "starve" the lethal cancer cells to death by depriving them of a specific nutrient that they require for survival.

In most cancers, this nutrient "drug of choice" is glucose. Pancreatic cancer, however, thrives on "consuming" the amino acid glutamine, which helps build muscle mass and is used by some cells for energy.

When cancer metabolizes excess amounts of glutamine, it can lead to extreme weight loss by robbing other cells of this important nutrient, a condition from which many pancreatic cancer patients suffer.

The excess glutamine results in cancers resistant to standard forms of chemotherapy.

Van Dang notes that "Penn's researchers have identified that autophagy" -- self-eating organisms -- "trigger the onset of pancreatic cancer. We have launched a clinical trial to stop the self-eating with a drug that has been used against malaria.

"We have also put this toward tweaking the immune system to fight off pancreatic cancer."

Dr. Charlie Yeo, chair of surgery and pancreatic cancer expert affiliated with the Thomas Jefferson University and Hospital in Philadelphia, cautions that Jobs died of a variation of pancreatic cancer, and he did not have a classic textbook case or assume traditional treatment.

Although high-profile cases draw awareness to the issue, Yeo says that less-famous, long-term survivors who have lived years past their diagnoses can serve as beacons of successful treatment.

He cites the October issue of National Geographic as required reading for finding out more about the disease. "Four of the five deadliest cancers listed which received the most significant amount of funding and support showed a steady decline in death rates over time. Not so for pancreatic, which has less funding and whose death rates had not declined," he says.

Yeo says that Ashkenazi Jews are at a slightly higher risk for the disease, especially in families with previous occurrences of breast and other forms of cancer.

Says Yeo, who was part of a team at Johns Hopkins to discover the DNA aspects of pancreatic cancer, "unlocking the genetic code to this cancer has not provided substantive benefit to patients" but it still provided useful information for future research.

Yeo asserts that there are several breakthroughs poised to emerge out of laboratories at Jefferson, under the leadership of Dr. Jonathan Brody, known in the field for developing novel therapeutic strategies to combat the cancer's chemical triggers.

Brody's use of molecular biology techniques includes gene knockout -- making the gene associated with causing the disease inoperative, done in the test tube -- and silencing assays -- switching off a gene through cell manipulation -- as well as development of a drug metabolism assay, detoxing through biochemical changes appplied to drugs.

Researchers at Penn's Abramson Cancer Center and the Perelman School of Medicine are now making public the breakthroughs they've had with pancreatic cancer treatments that activate the immune system to destroy the cancer's protective "scaffolding," which allows it to spread and do damage.

Early test subjects include a small group of patients with advanced pancreatic cancer, several of whose tumors shrank substantially. The team believes their findings could lead to quicker, less expensive cancer drug development.

"Until this research, we thought the immune system needed to attack the cancer directly in order to be effective," explains senior study author Dr. Robert H. Vonderheide, associate professor of hematology and oncology.

"Now, we know that isn't necessarily so. Attacking the dense tissues surrounding the cancer and tumor tissue is another approach, similar to attacking a brick wall by dissolving the mortar in the wall."  

 

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