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Study provides insight into pancreatic cancer progression, new target for treatment

12.06.2012
Mystery of how pancreatic cancer escapes immune detection is unraveled, offering hope for treatment

Researchers at NYU School of Medicine have made a key discovery that could help doctors treat one of the deadliest cancers.

A new study reveals a strategy used by pancreatic cancer cells to tinker with the immune system in a way that enables them to escape destruction by specialized immune cells.

The study, funded by the National Institutes of Health, The Pancreatic Cancer Action Network and by The Irvington Institute Postdoctoral Fellowship Program of the Cancer Research Institute, appears in the June 12 issue of Cancer Cell.

Pancreatic cancer is known for its aggressive nature. Only four percent of patients survive past five years from the time of diagnosis, and currently available therapies are largely ineffective.

"It is extremely important that we learn how the advancement of pancreatic cancer is being regulated in an effort to interrupt the progression of the disease," said senior author Dafna Bar-Sagi, PhD, senior vice president and vice dean for Science and chief scientific officer at NYU School of Medicine.

Using mouse models of pancreatic cancer, Dr. Bar-Sagi and colleagues found that a mutation of the KRAS gene, present in 95 percent of all pancreatic cancers, triggers the expression of a protein called GM-CSF. The tumor-derived GM-CSF then directs accumulation of myeloid-derived suppressor cells in the area surrounding the tumor. These cells suppress the body's natural immune defense reaction to growing tumor cells. In this way, pancreatic cancer cells escape being seen by the body's immune system and are free to grow and divide. Establishment of an immunosuppressive environment around pancreatic cancer cells, therefore, prevents their prompt rejection by the immune system.

By blocking production of GM-CSF in pancreatic cancer cells, the researchers found that they were able to disrupt accumulation of myeloid-derived suppressor cells, liberating the tumor-killing immune response. "Our study suggests a therapeutic strategy for harnessing the anti-tumor potential of the immune system," Dr. Bar-Sagi explained.

"Our findings should be applicable to a significant proportion of human pancreatic cancer cases, as the vast majority of human pancreatic cancer samples that we tested express the GM-CSF protein prominently," Dr. Bar-Sagi added. The researchers are hopeful that their findings will open new doors in therapeutic research, eventually leading to new drug therapies that block the production or function of the GM-CSF protein to allow anti-tumor immune cells to attack the cancer cells and halt tumor development.

Although the study focuses on pancreatic cancer, KRAS mutations are prevalent in a number of other cancers, including colon and lung cancer. "From a research standpoint, the contribution of KRAS mutation to the production of GM-CSF is a very exciting find, as it may have important implications for the therapeutic management of other cancers, as well," Dr. Bar-Sagi said.

Co-authors on the study include first author Yuliya Pylayeva-Gupta, PhD, Kyoung Eun Lee, PhD, Cristina H. Hajdu, MD, and George Miller, MD, all of NYU School of Medicine.

About NYU School of Medicine:

NYU School of Medicine is one of the nation's preeminent academic institutions dedicated to achieving world class medical educational excellence. For 170 years, NYU School of Medicine has trained thousands of physicians and scientists who have helped to shape the course of medical history and enrich the lives of countless people. An integral part of NYU Langone Medical Center, the School of Medicine at its core is committed to improving the human condition through medical education, scientific research and direct patient care. The School also maintains academic affiliations with area hospitals, including Bellevue Hospital, one of the nation's finest municipal hospitals where its students, residents and faculty provide the clinical and emergency care to New York City's diverse population, which enhances the scope and quality of their medical education and training. Additional information about the NYU School of Medicine is available at http://school.med.nyu.edu/.

Jessica Guenzel | EurekAlert!
Further information:
http://www.nyumc.org

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