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Stress granules may drive pancreatic cancer linked to obesity

by Pragati Singh

Obesity is known to raise the risk of getting at least 13 distinct types of cancer because it generates a chronic inflammatory state. For years, one scientist has questioned if there is more to the story than just inflammation.

Obesity may have a new role in the development of pancreatic cancer, which has an 11% five-year survival rate for most patients, according to current study from Dr Elda Grabocka’s group. Researchers observed that stress granules are substantially more abundant in patients with pancreatic cancer associated to obesity than in non-obese people in a study published in Cancer Discovery.

More crucially, scientists observed that inhibiting the creation of these granules inhibited the progression of cancer in rats. The research proposes a novel method to developing cancer medicines.

“Stress granule research is blossoming right now, but there’s still a lot we don’t know about what they’re comprised of and how they operate,” says Dr. Grabocka, an assistant professor at Thomas Jefferson University and a researcher at the Sidney Kimmel Cancer Center – Jefferson Health. “This is the first study to show that an excess of stress granules promotes tumour formation in the pancreas. In the lab, our mouse trials revealed a full reversal of cancer progression.”

The stress granule is a distinct sort of cellular compartment. The cell develops these non-membrane organelles in reaction to stress and to prevent self-destruction caused by stress. This cellular response and defence mechanism is found in both the animal and plant worlds. To protect their cells, tomato plants produce stress granules. Researchers do not yet know the makeup of these organelles or the specific process by which they safeguard the cell. However, it is clear that cancers have hijacked this defence system for their own ends. Many cancers produce much more stress granules than normal cells in order to prevent cancer cells from initiating a natural self-destruction cycle.

In light of this, Dr. Grabocka’s laboratory created a cancer mouse model that blocked the formation of stress granules in pancreatic cancer mice. When the genes governing the generation of stress granules were knocked off in mice, pancreatic cancer development was decreased by 50%.

According to Dr. Grabocka, obesity affects two-thirds of all persons in the United States and 50% of people globally. “We now had two options for dealing with the obesity issue.” It also increases the risk of other cancers and doubles the death rate from pancreatic cancer. Obesity is connected to pancreatic cancer in around 33% of instances, a figure that is expected to climb over the next several decades.

Pancreatic cancer was studied in two types of obese mice models: one that was genetically predisposed to overeating and the other that was fed a high-fat diet. Both animals’ tumours contained five to eight times the amount of stress granules found in non-obese mice. This led us to believe that the development of tumours in obese mice may be influenced by stress granules. When the cause of a cancer’s survival is gone, the cancer dies.

According to Dr. Grabocka, the benefits of inhibiting stress granule production in these obese mice with pancreatic cancer were completely unexpected. “We either saw no cancer development or between 1/14 and 1/20 the amount of growth we’d see” in obese mice with intact stress granules in the tumours.

The most significant difference was their overall survival rate. Mice die after 50-60 days in these pancreatic cancer models. After 300 days, 40% of obese mice with blocked tumour stress granules remained cancer-free, with no other signs of sickness in their bodies. “This level of reaction is quite unusual,” says Dr. Grabocka.

These investigations found that stress granules were not only present in cancer cells, but also had a role in cancer’s beginning development. This is the first clear indication, according to Dr. Grabocka, that stress granules contribute to the development of cancer.

Dr. Grabocka’s group has uncovered pharmaceutical targets that might limit the development of stress granules in pancreatic cancer induced by obesity.

The next step will be to test already existing small-molecule inhibitors to see if they can be used in humans.

According to Dr. Grabocka, cellular stress circumstances such as obesity increase the quantity of stress granules in cells and may be the cause of pancreatic and other cancers. “Because of the large effect we detect, researchers believe that targeting the production of stress granules might be a potential option for innovative cancer therapy.” Our findings pave the way for a human clinical trial.

Also Read: Heart medicine may be potential solution for alcohol consumption disorder: Research

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