Melanoma mutation likes fat for fuel

Cancer cells love glucose, the simple sugar the body uses for energy, so a high-fat, low-carb diet should starve them, right?

Where does this idea come from? Most cancer cells display enhanced glucose uptake, a phenomenon known as the Warburg effect, after 1931 Nobel Prize winner Otto Warburg.

Resurgent interest in exploiting the Warburg effect was described by Sam Apple in NYT Magazine and by Bret Stetka for NPR. High-fat, low-carb “ketogenic” diets are known to be effective against some types of epilepsy, and have also been explored by endurance athletes. Ketogenic diets have been tried as a clinical countermeasure against cancer in a limited way, mainly in brain cancer.

Before everybody gets too excited, let’s think about how particular cancer-driving mutations affect cell metabolism, suggests Winship Cancer Institute researcher Jing Chen. His team’s work in mice suggests that cancers with a common melanoma mutation (BRAF V600E) will grow faster in response to a ketogenic diet. In addition, the Winship researchers found that lipid-lowering agents such as statins curb these cancers’ growth, even in the context of a more normal diet.

The results were published on January 12 in Cell Metabolism.

Caveats: the findings cover just one mutation and need to be tested clinically.

Consumers and cancer patients already get a lot of advice about the right diet to fight cancer, but this research points toward an intriguing concept:  a “precision diet,” tailored to an individual patient’s cancer. 

“While human cancers share some common metabolic properties, they may also have distinct sensitivities depending on their oncogenic mutation profiles,” Chen says. “For certain mutations, it could be possible to design dietary regimens that may prevent or delay tumor progression.”

A possible implication of the results is that people fighting a cancer with a BRAF V600E mutation should avoid very low-carb diets. This mutation is found in more than 60 percent of melanomas and all of the hairy cell type of leukemia, as well as a subset of colorectal cancers (10 percent) and multiple myelomas (5 percent). Drugs are available that target the BRAF V600E mutation, but resistance to the drug usually develops.

“Limiting dietary fat intake and monitoring circulating acetoacetate levels might be beneficial in patients with BRAF V600E melanoma or other related cancers,” Chen says. “At this point, we can’t be specific about diet suggestions, because we need to know more about what types of dietary fat trigger acetoacetate production.”

“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 pre-malignancy and cancer settings,” Chen adds.

Previous paper on BRAF V600E mutation and acetoacetate here.

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Posted on by Quinn Eastman in Cancer Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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