Pancreatic cancer links to cholesterol

Pancreatic cancer links to cholesterol

Pancreatic cancer cells are so dependent on cholesterol, researchers have found genetic evidence that they can create their own, while others claim blocking it is crucial.

Two studies shed new light on pancreatic cancer growth and spread.

First, although all cells need cholesterol for the health of their membranes, researchers at Fox Chase Cancer Center have shown (1) for the first time that pancreatic cancer cells are dependent on cholesterol metabolism to form and grow. And by eliminating cholesterol production in the pancreas, they significantly slowed the progression of the disease.

They also felt that there was a possibility to target the enzyme that was involved in producing the cholesterol in the pancreas.

The study was led by Dr Igor Astsaturov and Dr. Linara Gabitova. Astsaturov said that cancers with activated EGFR and KRAS signalling have increased demands for cholesterol, and are vulnerable to interference with its delivery to the cancer cells.

The second study (2) from Cold Spring Harbor Laboratory showed that pancreatic cancer cells make far more cholesterol than they actually need for their membranes. And it just keeps being churned out and stored in the cells.

Somehow, the researchers felt the pancreatic cancer cells seemed to thrive on this overgrowth and storing of cholesterol, possibly due to enzymes involved in the process.

One such enzyme, called sterol O-acyltransferase 1 (SOAT1), which converts free cholesterol to its stored form and which pancreatic cancer cells have in abundance, is the driving force. By blocking this through genetic manipulation, the research team stalled the cancer’s growth. Interestingly this only occurred if the cells had a pair of damaged p53 genes – so it did not affect healthy pancreatic cells.

The researchers talked about SOAT being a target for drugs, but how many years would we need to wait.

In recent years pancreatic cancer rates have been rising, and experts feel the rise in rates of obesity, type-2 diabetes and high cholesterol are not merely coincidence. Pancreatic cancer is likely to become the second leading cause of cancer-related death by 2030.

Go to: Can statins really increase cancer survival?


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References

  1. Genetic Evidence links Pancreatic cancer and cholesterol
  2. “SOAT1 promotes mevalonate pathwaydependency in pancreatic cancer,” ; Journal of Experimental Medicine; David Tuveson, MD, PhD,

 


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