Prevention of Dietary-Fat-Fueled Ketogenesis Attenuates BRAF V600E Tumor Growth.
Level 5 - mechanism / opinion, no new human data
Preclinical animal (mouse xenograft) mechanism study with no human data
PubMed 28089569 · doi:10.1016/j.cmet.2016.12.010
What was done
Researchers evaluated the effect of a high-fat ketogenic diet on serum acetoacetate levels and tumor growth using human BRAF V600E melanoma xenograft mouse models. They also tested whether lowering acetoacetate with hypolipidemic agents or blocking acetoacetate-BRAF V600E binding using the homolog dehydroacetic acid would inhibit tumor progression.
What was found
The high-fat ketogenic diet elevated circulating acetoacetate and promoted tumor growth of BRAF V600E-expressing melanoma cells in mice. Conversely, reducing acetoacetate with hypolipidemic drugs or antagonizing its binding with dehydroacetic acid attenuated tumor growth. The abstract does not provide specific numerical values, sample sizes, or effect sizes.
Why it matters
This study provides a mechanistic link between dietary-fat-induced ketogenesis and accelerated growth in BRAF V600E-mutated melanoma, suggesting that dietary recommendations like the ketogenic diet may need to be tailored to specific tumor oncogenic profiles.
Limits
The findings are strictly preclinical in mouse xenograft models and cannot be assumed to translate directly to human patients. The abstract omits sample sizes, quantitative measurements, dosing regimens, and adverse effect profiles.
Cited by
- context Melanoma cell lines harboring the BRAF V600E mutation can use acetoacetate as an energy source and for biosynthetic reactions.