Researchers have found that a particular mutation in melanoma and other types of cancer is fueled by a high-fat diet.
Typically, cancer cells thrive on glucose, the body's simple sugar of choice for energy, so it was thought that diet high in fat but low in carbohydrates can keep the disease at bay. However, in a study published in the journal Cell Metabolism, researchers have shown that the BRAF V600E mutation will show faster growth in response to high-fat diets.
Jing Chen, Ph.D. and colleagues only explored just one mutation but the results of their work point to the possibility of a "precision diet" being used to help treat cancers individually.
"For certain mutations, it could be possible to design dietary regimens that may prevent or delay tumor progression," explained Chen.
Cancer Growth And Development
Cancer cells showing preference for glucose and taking up more of the simple sugar is referred to as a phenomenon called the Warburg effect. Diets low in carbohydrates have been used as a clinical countermeasure but the results of the current study show that those who fight cancer should take the other route and do away with low-carb diets.
BRAF V600E occurs in over 60 percent of all melanomas and is found in all of the hairy cell types of leukemia. In colorectal cancers, the mutation is present in 10 percent of cases, while 5 percent of multiple myelomas also have it. There are drugs designed to target BRAF V600E but resistance commonly develops.
Ketogenesis And Acetoacetate
During ketogenesis, fat is broken down by the body for energy. This usually occurs when blood glucose levels are low and results in the production of an alternate energy source: acetoacetate. In cancer cells with the BRAF V600E mutation, production of acetoacetate is stimulated. The energy source also binds mutated proteins and promotes oncogenic activity, promoting a cycle.
To test if cancer cells with the mutation would respond to external sources of acetoacetate, the researchers fed mice with diets where over 90 percent of calories were from fat. Mice with grafted tumors showed increased cancer cell growth while those with tumors from melanoma cells with other oncogenic mutations did not exhibit the same.
Additionally, the researchers observed that drugs that lower lipids, such as statins, fenofibrate, and niacin, were able to slow down the growth of BRAF V600E tumors even when mice were fed normal diets. Acetoacetate levels also dropped when lipid-lowering drugs were used.
Diet And Cancer Treatment
The researchers said they can't provide specific diet suggestions at the moment because there is more to be learned about what sort of dietary fat triggers the production of acetoacetate. They also noted that dehydroacetic acid, a chemical structurally similar to acetoacetate, is capable of limiting acetoacetate-related tumor growth in cancer cells with the V600E mutation. However, the chemical's anti-cancer properties still have to be studied, especially if it could alter cellular metabolism.
Chen and colleagues' work received funding support from the Winship Cancer Institute, the Jamie Rabinowitch Davis Foundation, Charles Harris Run for Leukemia, the Melanoma Research Foundation, the T.J. Martell Foundation, the Joel A. Katz Music Medicine Fund, and the National Cancer Institute.
