Combination therapy may enhance gemcitabine activity

February 28, 2012

PHILADELPHIA -- Oncologists who treat patients with pancreatic cancer may be one step closer to understanding why gemcitabine, the only currently available treatment, works in some cases but not in others, according to a paper in Cancer Discovery, a journal of the American Association for Cancer Research.

David Tuveson, M.D., Ph.D., a professor of pancreatic cancer medicine at the University of Cambridge, utilized a laboratory model to test the combination of gemcitabine and nab-paclitaxel in pancreatic cancer.

"The combination has shown promise in an early clinical trial, and clinical results from a pivotal phase III trial will be reported in 2013," said Tuveson. "However, we know very little about the mechanism of action because tumor samples have been so small."

Using a laboratory model of metastatic pancreatic ductal adenocarcinoma, the researchers showed that combination treatment increased intratumoral gemcitabine levels due to a marked decrease in the primary gemcitabine metabolizing enzyme, cytidine deaminase.

Paclitaxel appeared to reduce these levels through reactive oxygen species-mediated degradation, resulting in increased stabilization of gemcitabine. Tuveson said understanding these mechanisms of action are important and will lead to better administration of the therapeutic combination if the larger human trials prove positive.

"For example, we predict from this mechanistic study that nab-paclitaxel may be most effective if we administer it first, and delay administration of the gemcitabine. The next step is to test this prediction, since it could help a great deal with patient treatment," said Tuveson.
-end-
Follow the AACR on Twitter: @aacr #aacr
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the AACR

Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR's membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policy makers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

American Association for Cancer Research

Related Pancreatic Cancer Articles from Brightsurf:

Precision chemo-immunotherapy for pancreatic cancer?
Pancreatic cancer is highly lethal: according to the National Cancer Institute, only about 10 percent of patients remain alive five years after diagnosis.

Nerves keep pancreatic cancer cells from starving
Pancreatic cancer cells avert starvation by signaling to nerves, which grow into dense tumors and secrete nutrients.

Pancreatic cancer: Subtypes with different aggressiveness discovered
To date, no targeted personalized therapies for pancreatic cancer exist.

Bringing the 'sticky' back to pancreatic cancer
A multidisciplinary team of researchers at Japan's Tohoku University has found that a gene regulator, called BACH1, facilitates the spread of pancreatic cancer to other parts of the body.

Does lung damage speed pancreatic cancer?
High levels of CO2 in the body, due to chronic respiratory disorders, may exacerbate pancreatic cancer, making it more aggressive and resistant to therapy.

Scientists have identified the presence of cancer-suppressing cells in pancreatic cancer
Researchers have identified cells containing a protein called Meflin that has a role in restraining the progression of pancreatic cancer.

Pancreatic cancer discovery reveals how the aggressive cancer fuels its growth
A new discovery about pancreatic cancer sheds light on how the cancer fuels its growth and may help explain how promising cancer drugs work -- and for whom they will fail.

Overcoming resistance in pancreatic cancer
In pancreatic cancer cells' struggle to survive, the cells choose alternative routes when their main pathways are blocked by drugs.

Exposing how pancreatic cancer does its dirty work
Pancreatic cancer is a puzzle -- tumors slough off cells into the bloodstream early in the disease, but the tumors themselves have almost no blood vessels in them.

Targeting cell division in pancreatic cancer
Study provides new evidence of synergistic effects of drugs that inhibit cell division and support for further clinical trials.

Read More: Pancreatic Cancer News and Pancreatic Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.