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.