Do High-Fat Diets Fuel BRAF V600E Mutation-Harboring Melanomas?

Dietary fat intake might promote the growth of melanoma tumors harboring BRAF V600E mutations, and lipid-lowering drugs can slow that growth, according to a mouse study published in the journal Cell Metabolism.

“While human cancers share some common metabolic properties, they may also have distinct sensitivities depending on their oncogenic mutation profiles,” said senior study author Jing Chen, PhD, of Emory University’s Winship Cancer Institute in Atlanta.

“Lipid-lowering agents may have a role in cancer prevention or supplemental treatment approaches to reduce cancer progression or improve clinical outcomes in the BRAF V600E-positive premalignancy and cancer settings,” Dr. Chen said.

Among mice for which fats represented more than 90% of dietary calories, V600E-mutant melanoma tumor grafts grew to twice as large at 4 weeks after engraftment as those of mice on fed a normal diet. Dietary fat was not associated with tumor growth in melanoma xenografts that lacked this mutation, however.

By increasing circulating concentrations of acetoacetate, high-fat diets can increase the growth potential of BRAF V600E melanoma tumor growth in mice, the researchers believe.

The statin fluvastatin, niacin, and fenofibrate were associated with reduced acetoacetate levels and slowed tumor growth, the researchers reported. Injected acetoacetate led to hastened tumor growth after these lipid-lowering pharmacotherapies. An acetoacetate analogue, dehydroacetic acid, also inhibited acetoacetate’s effects on V600E tumor growth, they noted.

Scientists have long recognized that most tumor cells consume more glucose than normal cells, leading to suggestions and limited clinical study of low-carbohydrate diets for cancer patients as a way to deprive tumors of needed energy.

But the new findings suggest that the connection between diet and oncogenes is more complex that many have suspected-and that low-carb diets could prove to be counterproductive for patients with BRAF V600E-mutation-positive tumors.

If confirmed and clinically validated, such findings might suggest that efforts to develop precision oncology should involve “precision diet” for patients.

“For certain mutations, it could be possible to design dietary regimens that may prevent or delay tumor progression,” Dr. Chen added.

The BRAF V600E mutation is common in melanomas and hairy-cell leukemia, and is also sometimes found in colorectal cancer and multiple myeloma.