Featured Research

from universities, journals, and other organizations

Scientists break through pancreas cancer treatment barrier

Date:
March 19, 2012
Source:
Fred Hutchinson Cancer Research Center
Summary:
Pancreas cancer tumors spread quickly and are notoriously resistant to treatment, making them among the deadliest of malignancies. Their resistance to chemotherapy stems in part from a unique biological barrier the tumor builds around itself. Now scientists have found a way to break through that defense, and their research represents a potential breakthrough in the treatment of pancreas cancer.

Pancreas cancer tumors spread quickly and are notoriously resistant to treatment, making them among the deadliest of malignancies. Their resistance to chemotherapy stems in part from a unique biological barrier the tumor builds around itself. Now scientists at Fred Hutchinson Cancer Research Center have found a way to break through that defense, and their research represents a potential breakthrough in the treatment of pancreas cancer.

Related Articles


In a paper to be published in the March 20 issue of Cancer Cell, senior author Sunil Hingorani, M.D., Ph.D., an associate member of the Hutchinson Center's Clinical Research and Public Health Sciences divisions, and colleagues describe the biological mechanisms of how the tumor barrier is formed and detail a newly discovered way to break it down. Their research significantly increased the length of survival in a genetically engineered mouse model of the disease. Early clinical trials in humans are under way at a few sites in the U.S. and Europe, including Seattle Cancer Care Alliance, the Hutchinson Center's patient treatment arm.

Using a mouse model developed by Hingorani, the scientists combined gemcitabine, the current standard chemotherapy used to treat pancreatic ductal adenocarcinomas, with an enzyme called PEGPH20. When they infused the combination into specially engineered mice whose pancreas tumors mimic those of human pancreas cancer, the combination broke down the matrix barrier within the tumors and allowed the chemotherapy to permeate freely and spread throughout the cancerous tissue. The result was a 70 percent increase in survival time of the mice after the start of treatment, from 55 to 92 days.

"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," Hingorani said.

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 fibroinflammatory 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 pancreas cancer cells.

Hingorani and colleagues discovered that the fibroinflammatory 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.

"That's the primary reason pancreas cancers are resistant to everything we've thrown at them: because none of the drugs get into the tumor. It's physics first, before we even get to the intrinsic biology," Hingorani said.

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.

"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," Hingorani said.

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 from the University of Washington and the Translational Genomics Research Institute in Scottsdale, Ariz., contributed to the study.

Details about the open clinical trial can be found here: http://clinicaltrials.gov/show/NCT01453153


Story Source:

The above story is based on materials provided by Fred Hutchinson Cancer Research Center. Note: Materials may be edited for content and length.


Cite This Page:

Fred Hutchinson Cancer Research Center. "Scientists break through pancreas cancer treatment barrier." ScienceDaily. ScienceDaily, 19 March 2012. <www.sciencedaily.com/releases/2012/03/120319133904.htm>.
Fred Hutchinson Cancer Research Center. (2012, March 19). Scientists break through pancreas cancer treatment barrier. ScienceDaily. Retrieved January 29, 2015 from www.sciencedaily.com/releases/2012/03/120319133904.htm
Fred Hutchinson Cancer Research Center. "Scientists break through pancreas cancer treatment barrier." ScienceDaily. www.sciencedaily.com/releases/2012/03/120319133904.htm (accessed January 29, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, January 29, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Malnutrition on the Rise as Violence Flares in C. Africa

Malnutrition on the Rise as Violence Flares in C. Africa

AFP (Jan. 28, 2015) Violence can flare up at any moment in Bambari with only a bridge separating Muslims and Christians. Malnutrition is on the rise and lack of water means simple cooking fires threaten to destroy makeshift camps where people are living. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Poultry Culled in Taiwan to Thwart Bird Flu

Poultry Culled in Taiwan to Thwart Bird Flu

Reuters - News Video Online (Jan. 28, 2015) Taiwan culls over a million poultry in efforts to halt various strains of avian flu. Julie Noce reports. Video provided by Reuters
Powered by NewsLook.com
Media Criticizing Parents For Not Vaccinating Children

Media Criticizing Parents For Not Vaccinating Children

Newsy (Jan. 28, 2015) As the Disneyland measles outbreak continues to spread, the media says parents who choose not to vaccinate their children are part of the cause. Video provided by Newsy
Powered by NewsLook.com
Shark Bite Victim Making Amazing Recovery

Shark Bite Victim Making Amazing Recovery

AP (Jan. 27, 2015) A Texas woman who lost more than five pounds of flesh to a shark in the Bahamas earlier this month could be released from a Florida hospital soon. Experts believe she was bitten by a bull shark while snorkeling. (Jan. 27) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins