- Colon cancer screening looks for the presence of polyps, some of which can become cancerous.
- One type of serrated adenoma is thought to be precancerous and can recur after removal, particularly leading to invasive colon cancer.
- In preclinical studies, researchers discovered a mechanism that causes these cancers that involves dysregulated cholesterol metabolism.
- This means that this cholesterol dysregulation may be a target for statins, and trials are being planned to investigate this further.
Colon cancer is
Screening for colon cancer is done with a fecal immunochemical test, which looks for blood in the stool that may come from polyps, or with a colonoscopy, which visualizes the polyps.
There is
- Hyperplastic polyps are usually benign
- Adenomatous polyps (adenomas), which can turn into cancer.
Treatment usually involves removing these polyps.
A particular type of polyp known as a serrated adenoma is thought to be precancerous and must be removed completely.
This poses a challenge because the polyp is flat rather than growing in a stalk like other polyps and is difficult to visualize due to this and the part of the colon in which the polyp appears.
Cancer consisting of this type of polyp
Until now, it was unclear exactly why this particular type of polyp is more likely to cause cancer than others, but now a group of scientists at Weill Cornell Medicine in New York have discovered that metabolic A mechanism has been proposed.
Their research results are nature communications December 13, 2023.
Previous research Several members of the team showed that serrated adenoma polyps had lower levels of the protein kinase C (PKC) enzyme, which is involved in the regulation of numerous genes involved in cell proliferation, among other cellular metabolic pathways. The cells also evaded the body’s immune system, allowing cancerous tumors to grow. ”
In the latest study, researchers used a previously developed mouse model that developed serrated lesions in the colon.
The researchers first analyzed the genes transcribed in these tumor cells and found that despite the presence of high levels of cholesterol within the cells, cholesterol synthesis remained high in these cells. This suggested that cholesterol synthesis was dysregulated in these tumor cells.
Further analysis of mouse tumor cells showed that the loss of protein kinases led to activation of a transcription factor called SREBP2, which turns on cholesterol production.
Cholesterol is the powerhouse of many metabolic processes, and the study authors showed that cholesterol drives cancer in these cells and initiates tumor growth.
main author Professor Jorge Moscatoexplained the professor of pathology and laboratory medicine at Weill Cornell Medical College. Today’s medical news:
“When cholesterol is low, it is activated normally. This happens in every cell in the body. When cholesterol is low, SREBP2 is activated. And when cholesterol is high, SREBP2 is decreased.” This tumor cell In this case, the pathway is completely messed up, and while our cells know how to turn it on, they don’t know how to turn it off. In other words, SREBP2 is always activated, cholesterol is always produced, and cholesterol is always imported. ”
“So this gives this particular type of cancer cell a competitive advantage,” he added.
The researchers then used existing cell atlases to examine how well these results applied to human cells. They used these to examine gene activity in human serrated adenomas and found that only serrated adenomas, but not other types of colorectal tumors, had lower levels of the PKC enzyme and accumulated the transcription factor SREBP2. It turned out that there was.
Dr. Misag Karimisaid a medical oncologist who specializes in gastrointestinal cancers at City of Hope Orange County Lennar Foundation Cancer Center in Irvine, Calif., who was not involved in the study. MNT that “[t]The relationship between cholesterol and cancer is well-studied, and previous studies have shown that high cholesterol can trigger malignant cell activity and slow the immune response against cancer cells. ”
“Studies have also shown that changes in blood cholesterol levels are common to many cancers, but researchers are not sure whether these changes are the cause of the cancer or whether they are a result of the cancer. “We haven’t determined yet whether there is,” he said.
The scientists who conducted the study also organoid The levels of these metabolites are tested in the tumors of cancer patients. These were used to test the effectiveness of atorvastatin, a commonly prescribed statin, in inhibiting the proliferation of cells with low PKC levels.
Statins are among the most commonly prescribed drugs in the United States and many other countries and have been shown to reduce the risk of serious cardiac events by reducing the amount of cholesterol in the blood. Masu.
Professor Moscato and co-first author Professor Maria T. Diaz Mecosaid Professor of Oncology Pathology at Weill Cornell Medical College. MNT They planned to develop a clinical trial to determine whether statins could reduce the risk of cancer in patients with serrated adenoma.
Designing a trial to see if statins can help patients who have had their polyps removed would be a long-term study, since it takes about five years for polyps to come back.
“I think this would be a great chemotherapy prevention protocol or strategy. We’re just using statins. It’s that simple. You’re looking for a very sophisticated molecule, and you’re looking for something very simple. It’s like being found,” Professor Moscato said.
Dr. Camilli said there is growing evidence that statins may help reduce the risk of some types of cancer. “A 2020 study found evidence that statins can ‘starve’ cancer cells,” he said.
In 2019, Chinese researchers found that taking statins before diagnosis and
“Currently, statins are not commonly prescribed to reduce cancer risk,” Dr. Camilli cautioned. “There are millions of patients in the United States who take statins for high cholesterol, but the cancer prevention benefits of taking statins are not fully proven. Colorectal cancer. The best way to prevent it is to make healthy lifestyle choices and understand your own genetic risk for the disease.”