Navigation Links
Mayo Clinic researchers formulate treatment combination lethal to pancreatic cancer cells
Date:4/20/2009

DENVER - A combination of two targeted therapies packs a powerful punch to kill pancreatic cancer cells in the laboratory, Mayo Clinic cancer researchers report. With further testing of these drugs that are from classes of pharmaceuticals already used in patients, the Mayo research may lead to new treatment opportunities for patients with pancreatic cancer, which is extremely difficult to treat.

In a study being presented at the annual meeting of the American Association for Cancer Research, Mayo Clinic Cancer Center investigators found that rapamycin and panobinostat (also known as LBH589) act synergistically when used in combination, destroying up to 65 percent of cultured pancreatic tumor cells.

The finding is particularly significant, says the study's first author, Mamta Gupta, Ph.D., because the three cell lines studied were all resistant to the effects of chemotherapy - as are many pancreatic tumors - and because the drugs studied are already available for treatment of patients. Panobinostat is approved as therapy for cutaneous T cell lymphoma (CTCL), and rapamycin is best known as an immunosuppressant to help prevent rejection of transplanted organs.

"We need new therapies and strategies for the treatment of pancreatic cancer because these tumors are resistant to almost all known treatments," says Dr. Gupta, a research associate in the Division of Hematology. "No targeted treatment has shown much value to date."

Dr. Gupta studied the combination of agents in pancreatic cancer cells because her previous research at Mayo Clinic had shown that this combination worked well in laboratory tests of non-Hodgkin's lymphoma. A phase one clinical trial to test this combination in patients with lymphoma will open soon at Mayo Clinic under the direction of Thomas Witzig, M.D.

"While our pancreatic cancer cell line results look very promising, these are laboratory, not clinical, studies," she says. "We are preparing to take this combination of drugs to clinical trial to evaluate whether they can be safely given to patients."

While clinical studies will ultimately determine the benefits of panobinostat and rapamycin, Dr. Gupta and her colleagues remain focused on trying to understand the mechanism for how these agents together are so powerful.

Rapamycin and a closely related drug, everolimus (RAD001), have both been tested in pancreatic cancer cells, but by themselves have shown minimal activity, Dr. Gupta says. They belong to a class of agents known as mTOR inhibitors. The mTOR pathway is a major cellular survival mechanism that is persistently activated in pancreatic cancer cells.

In this study, rapamycin killed less than 5 percent of pancreatic cancer cells, and previous tests with RAD001 showed the same minimal effect, Dr. Gupta says. Panobinostat is a histone deacetylase (HDAC) inhibitor. In cancer, HDAC proteins "silence" tumor suppressor genes, so an HADC inhibitor restores expression of these beneficial genes. The agent is also believed to block angiogenesis - the growth of new blood vessels needed for tumors to grow," Dr. Gupta says.

Panobinostat killed about half of pancreatic cancer cells studied, she says. But both agents combined inhibited growth of pancreatic cancer cell lines and induced apoptosis (cell death) in up to 65 percent of the cells, Dr. Gupta says.

Dr. Gupta noted that panobinostat is effective at extremely low concentrations that are consistent with optimal pharmacological doses. "Our aim is always to use as little of a drug as possible in order to reduce potential side effects in patients," she says.

Although the researchers say they don't yet know the synergistic mechanism responsible for the combined drugs' effectiveness, they hypothesize that the agents are primarily interfering with the mTOR pathway, which is involved in growth and angiogenesis.

"Overall, these results indicate that rapamycin and panobinostat disrupts essential survival and proliferating pathways in pancreatic cancer cells, and this is a good start toward a novel treatment of this cancer," Dr. Gupta says.


'/>"/>

Contact: Karl Oestreich
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
Source:Eurekalert

Related medicine news :

1. Shared Health(R) Adds Practice Management Tools to Clinical Xchange(TM) Platform
2. Poniard Announces Publication of Results of Picoplatin Phase 2 Study in Journal of Clinical Oncology
3. Medarex Announces Clinical Data for MDX-1401 in Hodgkins Lymphoma at Annual Meeting of the American Association for Cancer Research
4. Chiltern Acquires Brazil-Based Clinical Research Organization Vigiun
5. Childrens Hospitals and Clinics of Minnesota Launches Series of Events to Benefit Cardiac Care
6. US releases updated clinical guidelines for HIV-associated opportunistic infections
7. University of Ottawa Heart Institute is North Americas First Clinical Site for Ultra-sophisticated X-Ray
8. Medifocus Inc. Reports Improved Clinical Efficacy for its Phase II, Randomized Clinical Study for the Treatment of Early Stage Breast Cancer Tumors
9. Leading Clinical Technology Organization M2S Inc. Announces the Appointment of Jeffrey Yablon as Senior Vice President, Business Development
10. Telik Announces Preclinical Presentations at AACR Annual Meeting
11. Clinical Diagnostic Lab Testing Market to Grow Over 90% through 2017
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a leading ... Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will revolutionize the rapidly ... CBD form that can be easily incorporated into liquid products, while reducing costs to ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Lori R. Somekh, ... member of ElderCounsel, a national organization of elder law and special needs planning attorneys. ... and rules. It also provides a forum to network with elder law attorneys nationwide,” ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... Many families ... However, many long-term care insurance companies have a waiver for care if the client ... elimination period, when the family pays for care, is often waived, so the benefits ...
(Date:10/13/2017)... ... , ... Ellevate Network, the leading network for professional women, brought together some ... at their inaugural Summit in New York City in June. The event was livestreamed ... over 3 million. To watch the Mobilize Women video, click here . ...
(Date:10/13/2017)... ... , ... Yisrayl Hawkins, Pastor and Overseer at The House of Yahweh, has ... least understood books in the Holy Scriptures, Revelation. The Book of Revelation paints a ... centuries. Many have tossed it off as mere rubbish, but Yisrayl Hawkins says that ...
Breaking Medicine News(10 mins):
(Date:10/4/2017)... , Oct. 4, 2017  South Korean-based healthcare ... CPR training aide "cprCUBE" on Kickstarter. The device will ... during cardiac arrests with better efficiency compared to the ... offers real-time feedback on efficacy of the compression for ... campaign has a goal to raise $5,000. ...
(Date:10/2/2017)...  AllianceRx Walgreens Prime, the combined central specialty pharmacy ... benefit manager Prime Therapeutics LLC (Prime), today officially began ... unveiling of new signage at its headquarters in ... a few other company-owned facilities across the country. This ... of whom will begin to see the AllianceRx Walgreens ...
(Date:9/27/2017)... , Sept. 27, 2017  Commended for their devotion to ... awards. Ranked as number one in the South Florida Business ... in Inc. 5000 yearly list, the national specialty pharmacy has ... Armando Bardisa will soon be honored by SFBJ as ... Set to receive his award in October, ...
Breaking Medicine Technology: