Hutchinson Center and TGen scientists discover potential ‘break through’ in pancreatic cancer

Scientists at Fred Hutchinson Cancer Research Center and the Translational Genomics Research Institute (TGen) have discovered a literal ‘break through’ in pancreatic cancer.

A unique biological barrier that pancreatic cancer tumors build around themselves have made them especially resistant to chemotherapy treatments, according to the Hutchinson Center/TGen study published today in the highly-regarded journal Cancer Cell.

Pre-clinical experiments show that a combination of drugs could break down the barrier surrounding these tumors, allowing chemotherapy drugs to freely spread and permeate throughout the cancerous tissue, according to the study.

“Discovering how to break through this barrier is a significant finding that could eventually enable therapeutic compounds to be much more effective in combating this deadly cancer and helping patients,” said Dr. Daniel Von Hoff, M.D., TGen’s Physician-In-Chief and one of the authors of the study, as well as one of the world’s leading authorities on pancreatic cancer.

“The barrier surrounding pancreatic ductal adenocarcinoma has prevented therapeutics from reaching and effectively acting on this cancer,” said Dr. Von Hoff, who also is head of TGen’s Clinical Translational Research Division.

This research is now being tested for the first time in patients in the U.S. and Europe, including those at Seattle Cancer Care Alliance, the Hutchinson Center’s patient treatment arm. These tests have the potential to significantly increase the length of survival in patients with pancreatic cancer, which is notoriously fast-spreading and among the most lethal of all cancers, the study says.

Dr. Sunil Hingorani, M.D., Ph.D., the study’s senior author and an associate member of the Hutchinson Center’s Clinical Research and Public Health Sciences divisions, developed the study’s laboratory model. By combining gemcitabine - the current standard chemotherapy used to treat patients’ pancreatic ductal adenocarcinomas - with an enzyme called PEGPH20, scientists showed that the tumor barrier could be broken down and the drug could more easily reach the cancerous tissue.

Pancreatic Cancer Diagnosis: What To Say and to Whom

Deciding whom to tell about your diagnosis and pancreatic cancer treatment is important, but you should also think about the possibility of the news reaching a wider circle. If you want to keep those in the know at a minimum, convey very clearly to everyone you inform that you expect the information to be kept confidential.

Coan advises telling your office’s human resources department if you work outside the home, but beyond that, be as private as you wish. Even if you do admit to a health problem, don’t feel you have to divulge details.

“Telling people you are facing a very difficult health situation but prefer not to go into details is enough,” she says. “It is human nature to jump to the worst case when hearing about pancreatic cancer, blurting out the name of the latest celebrity who died a terrible death. You have permission to spare yourself repetitions of this upsetting scenario by thanking people for their kind words and prayers, but [saying that] you are choosing to only share the details with close family and friends.”

“This represents the largest survival increase we’ve seen in any of the studies done in a preclinical model, and it rivals the very best results reported in humans,” Dr. Hingorani said. “Being able to deliver the drugs effectively into the tumor resulted in improved survival as well as the realization that pancreas cancer may be more sensitive to conventional chemotherapy than we previously thought.”

Unlike most solid tumors, pancreas tumors use a two-pronged defense to keep small molecules, such as those contained in chemotherapy, from entering: a vastly reduced blood supply and the creation of a strong fibro-inflammatory response. The latter includes the production of fibroblasts, immune cells and endothelial cells that become embedded within a dense and complex extracellular matrix throughout the tumor. One major component of this matrix is a substance called hyaluronan, or hyaluronic acid (HA). HA is a glycosaminoglycan, a complex sugar that occurs naturally in the body and is secreted at extremely high levels by pancreatic cancer cells.

Pancreatic cancer is a disease that occurs when cells of the pancreas, a gland located behind the stomach, grow uncontrollably, forming a tumor and inhibiting normal pancreatic function. Because the pancreas produces digestive enzymes needed to break down dietary fat, consuming fat increases the workload on the pancreas, causing stress on the gland that can increase the pain from pancreatic cancer.

Role of the Pancreas
The pancreas contains two types of cells; the islets of Langerhans that produce the hormones insulin and glucagon - important for maintaining blood glucose levels, and the acinar cells that produce enzymes important for digestion. The pancreas produces two protease enzymes, trypsin and chymotrypsin, that break down proteins; amylase enzyme that breaks down carbohydrates; and lipase enzyme that breaks down dietary fat. The pancreas secretes these enzymes with pancreatic fluid that flows through the pancreatic duct to the common bile duct and empties into upper portion of the small intestine known as the duodenum.

Dr. Hingorani, Dr. Von Hoff and their colleagues discovered that the fibro-inflammatory response creates unusually high interstitial fluid pressures that collapse the tumor’s blood vessels. This in turn prevents chemotherapy agents from entering the tumors. The researchers found that HA is the main biological cause of the elevated pressures that leads to blood vessel collapse.

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