Colorectal serrated polyps, often overlooked during colonoscopies, can develop into aggressive tumors responsible for a significant percentage of colorectal cancers.
Researchers at Weill Cornell Medicine have uncovered a critical link between the production of cholesterol and the development of these precancerous lesions and their associated tumors.
This groundbreaking discovery offers potential avenues for preventing and treating these aggressive colorectal tumors by targeting cholesterol production.
Serrated polyps are distinct precancerous lesions in the colon, characterized by their sawtooth appearance under a microscope. They are challenging to detect during routine colonoscopies, yet the tumors they can evolve into are highly invasive and resistant to treatment.
Understanding the underlying molecular mechanisms driving the formation of serrated polyps and tumors is crucial for developing effective prevention and treatment strategies.
Researchers conducted a preclinical study involving mice that develop serrated polyps and tumors. They examined the molecular events within these tissues that lead to increased cholesterol production.
This discovery was further validated through analyses of human serrated polyps and tumors. The study aimed to determine whether blocking cholesterol production could prevent the progression of these colorectal tumors.
The study revealed several critical findings:
Serrated-type tumors displayed a significant upregulation of cholesterol synthesis, suggesting that cholesterol may play a pivotal role in the early stages of tumor development.
The absence of specific enzymes (aPKCs) in gut linings, previously linked to serrated polyps and tumors, activated a transcription factor (SREBP2) responsible for increasing cholesterol production.
Tests on human colorectal polyp and tumor samples confirmed that serrated-type tumors exhibited low aPKC levels, concurrent with heightened cholesterol biosynthesis driven by SREBP2.
Combining two cholesterol synthesis-blocking drugs, including the commonly used atorvastatin, significantly reduced the formation of serrated polyps and tumors in preclinical models. Moreover, the tumors that did develop were less aggressive than untreated counterparts.
The study suggests that targeting cholesterol production may be an effective strategy for preventing and treating serrated-type colorectal tumors, which are notorious for their aggressiveness.
While previous trials using cholesterol-lowering drugs (statins) to prevent colorectal cancer yielded conflicting results, this research highlights the specific impact on serrated polyps and tumors.
The findings open the door to potential clinical trials involving cholesterol-lowering interventions for patients with serrated colorectal polyps.
By uncovering the critical role of cholesterol production in the development of serrated polyps and tumors, this study offers hope for preventing and treating these aggressive colorectal lesions.
Targeting cholesterol pathways may provide a novel approach to managing serrated-type colorectal tumors, potentially saving lives and improving patient outcomes.
Future clinical trials will be essential to validate the effectiveness of such interventions in human patients, offering a proactive method to combat this challenging form of cancer.
If you care about cancer, please read studies that artificial sweeteners are linked to higher cancer risk, and how drinking milk affects risks of heart disease and cancer.
For more health information, please see recent studies about the best time to take vitamins to prevent heart disease, and results showing vitamin D supplements strongly reduces cancer death.
The research findings can be found in Nature Communications.
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