Genetic Evidence Links Pancreatic Cancer and Cholesterol

PHILADELPHIA (March 16, 2017) — Researchers at Fox Chase Cancer Center have shown for the first time that pancreatic cancer cells are dependent on cholesterol metabolism to form and grow. The study, led by Igor Astsaturov, MD, PhD, and Linara Gabitova, PhD, also singled out an enzyme that could be targeted to eliminate cholesterol production within the pancreas. A poster of the study is being presented at the American Association for Cancer Research (AACR) Annual Meeting 2017 in Washington, DC on Sunday, April 2.

“In our study, eliminating cholesterol production in the pancreas significantly slowed pancreatic cancer progression” said Astsaturov. “The implication is that it may be possible to reduce the risk of pancreatic cancer.”

Working with a very aggressive genetic mouse model of pancreatic cancer known as KPC mice, Astsaturov and Gabitova compared cohorts that were bred to develop pancreatic cancer. In the experimental group, they created a conditional cholesterol pathway enzyme deficiency, effectively knocking out the mechanism for producing cholesterol within the pancreas. Some of the mice missing the ability to produce cholesterol did not develop cancer, and in cases where pancreatic cancer appeared, it appeared significantly later than it did in mice that were able to produce cholesterol.

This study built upon previously established data that cancers with activated EGFR and KRAS signaling have increased demands for cholesterol, and are vulnerable to interference with its delivery to the cancer cells.

In recent years pancreatic cancer incidence and death rates have been rising, coinciding with increasing rates of obesity and associated conditions, including type 2 diabetes and high cholesterol. Pancreatic cancer is projected to become the second leading cause of cancer-related death by 2030.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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