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.
"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.
Details about the open clinical trial can be found at: http://clinicaltrials.gov/show/NCT01453153.
Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Overall five-year survival is less than 5 percent with a median survival of four to six months.
Grants from the National Cancer Institute, the Giles W. and Elise G. Mead Foundation, Safeway and several individuals supported the research. Collaborators at the University of Washington also contributed to the study.
About Fred Hutchinson Cancer Research Center
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit http://www.fhcrc.org.
Press Contact:Dean Forbes
Steve Yozwiak | EurekAlert!
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy