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Hutchinson Center and TGen scientists discover potential 'break through' in pancreatic cancer
Date:3/20/2012

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.

"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.

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.

Administering the enzyme/gemcitabine combination degrades HA in the tumor barrier and results in rapid reduction of the interstitial fluid pressure. This in turn opens the blood vessels and permits high concentrations of chemotherapy to reach the tumor.


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Contact: Steve Yozwiak
syozwiak@tgen.org
602-343-8704
The Translational Genomics Research Institute
Source:Eurekalert

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