The abstract is read at the publisher; the summary is JClub's.
Redirecting intestinal cholesterol metabolism via gut microbiota generates 4-cholesten-3-one (4-C-3), which suppresses colorectal cancer growth and enables regression in preclinical models.
- Why it matters: Systemic cholesterol lowering has limited benefits and safety concerns, while excess cholesterol in colorectal cancer promotes progression; a safer, targeted strategy is needed.
- What they did: A microbial metabolite screen identified 4-C-3 as depleted in faecal and tumour samples from CRC patients; 4-C-3 was tested in CRC cell lines, patient-derived organoids, and xenografts.
- The result: 4-C-3 inhibited epidermal growth-factor receptor activation and stabilized mutant oncogenic KRAS in an inactive state, overcoming KRAS-driven resistance, and restoring 4-C-3 with Oscillibacter ruminantium or engineered Escherichia coli reduced intratumoral cholesterol and induced tumour regression without overt toxicity.
The findingWhy it mattersWhat they didThe result
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