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:6/27/2017)... ... June 27, 2017 , ... Excel ... Mike Finnegan to the position of Executive Vice President, Sales and Marketing. Finnegan ... technology, telehealth and medical device sales leadership. He has received industry recognition for ...
(Date:6/27/2017)... Philadelphia PA and London UK (PRWEB) , ... June 27, 2017 ... ... for applying to a clinical study is whether they can trust the sponsor to ... competitive, it is vital that sponsors and CROs establish payment strategies that encourage sites ...
(Date:6/27/2017)... ... June 27, 2017 , ... Salucro, the cloud-based payment ... care industry’s hospitals and provider groups, has announced that it will now offer ... Health is a San Francisco health-finance startup that has launched a series of ...
(Date:6/27/2017)... ... June 27, 2017 , ... Building on ... efforts, Louisiana became the sixth state to pass legislation which ensures that children ... Edwards’ signature, Louisiana joins the states of Alabama, Arizona, Florida, Utah and Washington ...
(Date:6/27/2017)... California (PRWEB) , ... June 27, 2017 , ... A ... has been projected to reach a staggering $6.81 billion by the year 2024 according ... rising at a faster rate than those made from titanium. Los Angeles area clinic ...
Breaking Medicine News(10 mins):
(Date:6/12/2017)... Kineta, Inc., a biotechnology company focused on the ... President of R&D and Head of Virology Kristin Bedard has ... the Northwest and Beyond meeting sponsored by Life Science ... from 8:30-10:30 AM PDT at the Agora Conference Center in ... Bedard will be joined by other leaders in infectious disease ...
(Date:6/9/2017)... , June 9, 2017 More than ... further effort to help spread lessons learned from clinical ... International Diabetes Federation (IDF) and Eli Lilly and Company ... the second phase of the Bringing Research in Diabetes ... their commitment to helping people with diabetes effectively manage ...
(Date:6/7/2017)... -- Endo International plc (NASDAQ: ENDP ) ... Joseph R. Goodwin , U.S. District Court Judge for ... , entered a case management order in MDL 2325, ... Litigation (the "MDL") that includes a provision requiring plaintiffs ... on specific causation within one hundred twenty (120) days ...
Breaking Medicine Technology: