Navigation Links
Cancer research brief: Targeting pancreatic cancer drug resistance
Date:7/8/2013

Cold Spring Harbor, NY Pancreatic cancer is one of the most deadly and intractable forms of cancer, with a 5-year survival rate of only 6%. Novel therapies are urgently needed, as conventional and targeted approaches have not been successful and drug resistance is an increasing problem.

Previously it had been thought that poor penetration of the drugs into pancreas tumors was the main reason for treatment failure. But now a team of scientists led by Cold Spring Harbor Laboratory (CSHL) Professor David Tuveson M.D., Ph.D., shows there are other factors at work, too.

In a paper published online today in the Proceedings of the National Academy of Sciences, Dr. Tuveson's group shows that there are survival cues inside the pancreatic tumor mass. Molecules in the milieu around the cancer cells, such as Connective Tissue Growth Factor (CTGF), provide "pro-life" signals that overcome the killing power of chemotherapeutic drugs.

"In addition to drug delivery being a problem, there is also this nurturing aspect that prevents cancer cells responding to the drugs," says Tuveson.

But he and his colleagues may have found a way to prevent this. The antibody FG-3019, a molecule that is now in phase 1/2 clinical investigation as a treatment option for pancreatic cancer, binds to CTGF and prevents it from providing cells with survival cues. Those cues seem to be mediated, at least in part, through a molecule within the cell called XIAP (X-linked inhibitor of apoptosis). XIAP derives its name from its function -- an ability to help keep the cell alive by preventing a process called apoptosis, a form of cellular suicide.

The Tuveson lab used a novel mouse model for pancreatic cancer to test FG-3019. Tumors in mice treated with FG-3019 in combination with the chemotherapeutic drug gemcitabine stopped growing. Inside the tumor there was an increase in the amount of cancer cells dying through apoptosis, which was associated with a decrease in levels of XIAP. Importantly, mice treated with both FG-3019 and gemcitabine also had an increased lifespan.

This suggests that overcoming resistance to medicines in cancer may be possible using combination therapy -- co-administering molecules that help open up the tumor to drugs as well as other molecules that prevent cancer cell survival signals alongside the chemotherapeutics. Both CTGF and XIAP have been shown to be present in human pancreatic cancer tumors so combination therapy using antagonists of either molecule could be a feasible approach, says Tuveson.

There are other compounds that sensitize cancer cells to die, for example, antagonists of Bcl-2 and Bcl-xL, cellular proteins that prevent apoptosis. "These are pro-apoptosis medicines, so it's not impossible to imagine that one could target these types of pathways in cancer cells with drugs. We haven't done those studies yet but that would be the logical progression," says Tuveson, who is the Director of the Lustgarten Foundation Pancreatic Research Laboratory at CSHL and Director of Research for the Lustgarten Foundation.


'/>"/>

Contact: Edward Brydon
ebrydon@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

Related medicine news :

1. Study Suggests Vaccine May Help Kids With Brain Cancer
2. New Stool Test Might Aid in Early Detection of Colon Cancer
3. Study reveals how cancer drug causes diabetic-like state
4. How a cancer drug leads to diabetes
5. You Survived Cancer: Now Pay Attention to Your Overall Health
6. New drug prevents spread of human prostate cancer cells
7. Eliminating the good cholesterol receptor may fight breast cancer
8. Taller, Heavier Women May Face Higher Ovarian Cancer Risk
9. Experimental Chemo Combo for Colon Cancer Disappoints
10. Veggies Like Broccoli, Cabbage May Help Fight Breast Cancer: Study
11. Targeted therapeutics for colon cancer to be presented at AACR meeting
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/5/2016)... ... December 05, 2016 , ... ... at the 2016 Anti-Aging & Beauty Awards at The Aesthetic & Anti-aging ... Anti-aging Medicine European Congress (AMEC) brings together the industry’s leading scientific experts, ...
(Date:12/5/2016)... Columbus, OH (PRWEB) , ... December 05, 2016 ... ... novel engineering solution called the CardioQuick Patch® significantly improves the reproducibility and accuracy ... usability in various healthcare settings. , Over the last 60 years, studies ...
(Date:12/4/2016)... York, NY (PRWEB) , ... December 03, 2016 ... ... largest non-profit organization devoted exclusively to funding innovative lymphoma research and serving the ... services – hosted its first Swirl: A Wine Tasting Event in New York ...
(Date:12/4/2016)... ... December 03, 2016 , ... While James Earl Jones is known ... for in a show called "Front Page". One of the forthcoming episodes examines mammogram ... rates have plummeted in large part due to early detection. Like any other disease, ...
(Date:12/4/2016)... ... December 03, 2016 , ... ... Entrepreneurial Company in the Dallas area” Tuesday evening at the 26th Annual SMU ... presented by SMU's Cox School’s Caruth Institute for Entrepreneurship. Dallas 100™, co-founded by ...
Breaking Medicine News(10 mins):
(Date:12/4/2016)... 2016   Pairnomix, LLC, a genetic research company ... by the White House, today announced that findings from its ... of candidate therapies for a patient with epileptic encephalopathy caused ... presented at the 70 th Annual Meeting of the ... , December 2-6, 2016.  Pairnomix, unique process ...
(Date:12/4/2016)... , Dec. 3, 2016  Findings from ... safety of CTL019, an investigational chimeric antigen receptor ... pediatric and young adult patients with B-cell acute ... an oral session at the 58th American Society ... 3, 4:00-5:30 p.m.). The global Phase II study ...
(Date:12/2/2016)... British Columbia , December 2, 2016 bioLytical Laboratories, ... de la Compañía, el INSTI HIV Self Test , a los miembros ... ... INSTI HIV Self Test! (PRNewsFoto/bioLytical Laboratories) ...      (Photo: http://photos.prnewswire.com/prnh/20161201/444905 ) ...
Breaking Medicine Technology: