Navigation Links
Embryonic signal drives pancreatic cancer and offers a way to kill it
Date:11/3/2011

Pancreatic cancer is a particularly challenging one to beat; it has a tendency to spread and harbors cancer stem cells that stubbornly resist conventional approaches to therapy. Now, researchers reporting in the November issue of Cell Stem Cell, a Cell Press publication, have evidence to suggest there is a way to kill off those cancer stem cells. The target is a self-renewal pathway known for its role not in cancer but in embryonic stem cells.

"I don't think the cancer stem cells have any direct link to embryonic development, rather they are using this developmental pathway for their uncontrolled self-renewal capacity," said Christopher Heeschen of the Spanish National Cancer Research Centre in Madrid. "This pathway is completely inactive in adult tissue. We've checked many tissues and there is zero no detectable expression at all."

The so-called Nodal/Activin pathway's embryonic ties and absence from other tissues present a real opportunity. It suggests you could target the molecular pathway without harming other adult cells. Heeschen's team has now shown that approach to therapy does seem to work in mice.

They first demonstrated the important role of the Nodal/Activin pathway in cancer stem cells derived from human pancreatic cancer. When that signal was blocked, normally resistant pancreatic cancer stem cells became sensitive to chemotherapy.

The researchers then moved on to experiments in mice with established tumors seeded from human cancer cells. Treatment of those animals with the pathway inhibitor plus standard chemotherapy eliminated those stem cells.

"The dual combination therapy worked strikingly well," Heeschen said. "The mice responded with 100 percent survival after 100 days." That's compared to mice not receiving the therapy, which bore large tumors and died within 40 days of implantation.

That two-part treatment wasn't enough to tackle pancreatic cancer when intact tumor tissue was implanted into mice as opposed to just cancer cells, the researchers found. Heeschen says that's because those cells were nestled within a supportive "stroma." That protective tissue delivered the Activin signal and prevented the drug combination from reaching the cells.

To get around that, Heeschen and his colleagues added a third ingredient to therapy, an inhibitor intended to target the stroma. The three-pronged approach translated into long-term, progression-free survival for the mice.

Interestingly, Heeschen says the animals' tumors didn't show signs of shrinking even as they were defeated. "They were more or less dead tissue. They were senescent with no cancer stem cells just sitting there," he said.

Those tissues apparently had no ability to form new tumors. The findings suggest that tumor regression isn't always the key thing to look for. It also shows that drugs designed to target cancer stem cells alone are promising, but only in combination with other drugs.

"The concept that you can hit cancer stem cells and tumors will melt away must be abandoned," Heeschen said. "You have to treat the entire cancer - the stroma, cancer stem cells and differentiated cells - as a complex. "

Heeschen says there are hints that this embryonic pathway might have important roles in other forms of cancer, including breast, lung and colorectal cancers. That's something they will now test in further studies.


'/>"/>

Contact: Lisa Lyons
elyons@cell.com
617-386-2121
Cell Press
Source:Eurekalert

Related medicine news :

1. New model for studying germ cell tumors in testes enlists embryonic stem cells
2. Moving beyond embryonic stem cells: Encouragement on the horizon
3. Leftover embryonic cells connect gastric reflux and cancer
4. Embryonic stem cells help deliver good genes in a model of inherited blood disorder
5. Scientists Spot Genetic Areas Key to Embryonic Development
6. States Now Fund Most Embryonic Stem Cell Research in U.S.
7. First Patient Treated in U.S.-Approved Embryonic Stem Cell Trial
8. Most Americans Back Embryonic Stem Cell Research: Poll
9. Natural lung material is promising scaffold for engineering lung tissue using embryonic stem cells
10. Human embryonic stem cells purified in new, rapid technique
11. UCLA scientists isolate the first stages of tissue production in human embryonic stem cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2017)... , ... May 24, 2017 , ... Patients who want ... OH, can now meet with Dr. Joseph Bedich for a consultation, with or without ... improving their oral health and functionality. , Dr. Bedich offers a variety ...
(Date:5/24/2017)... , ... May 24, 2017 ... ... the female reproductive tract in which the endometrial lining of the uterus ... inflammation and pain. Patients experiencing painful intercourse, painful periods, pelvic pain, or ...
(Date:5/24/2017)... (PRWEB) , ... May 24, 2017 , ... ... practice is offering holistic pediatric dentistry options for its patients on Long Island, ... the patient’s entire physical well being, and is one of the biggest trends ...
(Date:5/24/2017)... Orange, NJ (PRWEB) , ... May 24, 2017 , ... ... for avoiding back injury when either lifting weights for strength training and exercise or ... Atlantic Spine Center . , “Body position is everything,” Dr. Chang says. “Improper technique ...
(Date:5/23/2017)... ... ... Allegheny Health Network and the Alexis Joy D’Achille Foundation ... at West Penn Hospital , a unique facility that will offer the most ... Construction of the Center is underway with a scheduled opening in the fall of ...
Breaking Medicine News(10 mins):
(Date:5/22/2017)... MAITLAND, Fla. , May 22, 2017 /PRNewswire/ ... industry as a whole continue to make the ... evidence becomes increasingly important for ensuring positive patient ... Key industry stakeholders are shifting focus away from ... results and effects of long-term specialty drug therapy ...
(Date:5/15/2017)... Enterin Inc., a privately-held CNS pharmaceutical company based ... to treat Parkinson,s disease (PD), has enrolled the first patient ... randomized, controlled, multicenter study involving patients with PD and taking ... over a 9-to-12-month period. The first stage is open label ... Participating sites include Denver , ...
(Date:5/10/2017)... -- Global Health Intelligence (GHI), the leading healthcare ... published its 2017 ranking of the Best-Equipped Hospitals in ... analysis from GHI,s hospitals database for Latin America , ... The GHI database covers 86% of the hospitals in ... points for each institution in key areas such as beds, ...
Breaking Medicine Technology: