Cholesterol plays roll in colon cancer tumor growth

Statins, primarily known for their cholesterol-lowering properties, might also play a role in preventing colon cancer tumor growth. Colon cancer, the third most prevalent cancer worldwide, can be screened for early detection, particularly through fecal tests and colonoscopies. Of particular interest are serrated adenomas, a pre-cancerous type of polyp that can lead to invasive colon cancers.
Researchers from Weill Cornell Medicine, NY, have discovered a mechanism driving these cancers, involving dysregulation of cholesterol metabolism. This discovery, published in Nature Communications on December 13, 2023, opens up the possibility that statins could target this dysregulation.
Serrated adenomas, which make up 15 to 30% of colorectal cancers, are particularly invasive and resistant to treatment. These polyps are flat and harder to visualize, posing a challenge in treatment.
Previous research identified that serrated adenoma polyps have lower levels of protein kinase C (PKC) enzymes, which regulate genes involved in cell proliferation. A study using a mouse model developed serrated lesions in the colon, revealing that cholesterol synthesis in these tumor cells was dysregulated.
Further analysis showed that the loss of protein kinases activated a transcription factor called SREBP2, which triggers cholesterol production. The study demonstrated that cholesterol was driving cancer growth in these cells.
The research team then examined human cell atlases to validate their findings in human serrated adenomas. They discovered that only serrated-type tumors had low levels of PKC enzymes and an accumulation of SREBP2.
Dr. Misagh Karimi, a medical oncologist not involved in the research, highlighted the evolving research area connecting cholesterol and cancer. Studies have shown that high cholesterol can trigger malignant cell activity and affect the immune response to cancer cells.
The researchers also tested the effectiveness of atorvastatin, a commonly prescribed statin, on organoids created from cancer patients’ tumors. These organoids had low levels of PKC, and atorvastatin inhibited their growth.
Professors Jorge Moscat and Maria T. Diaz-Meco, the lead authors of the study, are planning a clinical trial to determine if statins could lower cancer risk in patients with serrated adenoma. This trial would be a long-term investigation due to the time it takes for polyps to recur, if at all.
Dr. Kamiri noted that evidence is growing that statins could reduce the risk of several types of cancer. However, he cautioned that statins are not generally prescribed for cancer risk reduction, emphasizing the importance of healthy lifestyle choices and understanding genetic risks.
This research suggests that statins, beyond their role in managing cholesterol, might offer new avenues in cancer prevention, particularly for colorectal cancer arising from serrated adenomas.
—Hannah Flynn