Researchers have discovered a new approach to treating a particularly aggressive form of brain cancer, glioblastoma. They found that combining a special diet with a specific drug can help target and destroy the key cancer cells in this deadly disease. This breakthrough was published in the online edition of the Nature group journal Communications Biology.
The researchers, who come from various international institutions, experimented with a calorie-restricted diet that is high in fat and low in carbohydrates. They combined this diet with an antibiotic known as 6-diazo-5-oxo-L-norleucine (DON). The result was an effective method for tackling glioblastoma, a fast-spreading type of brain cancer that is often resistant to conventional treatments.
The diet, referred to as a ketogenic diet, and the antibiotic DON, which has been known since 1956, together offer a non-toxic strategy for managing this deadly brain cancer. Boston College Professor of Biology, Thomas N. Seyfried, and Boston College Senior Research Scientist, Purna Mukherjee, were lead authors of the study.
In their research, the team explored the idea that glioblastoma primarily involves a problem with how the cells in the brain produce energy. They proposed that it is linked to the fermentation process that happens in the mitochondria of these cells. This metabolic theory of cancer, in contrast to conventional genomic theories, suggests that the origin of cancer lies in these energy-producing structures.
To test this theory, the researchers used DON to inhibit the fermentation of a particular amino acid called glutamine. They combined this with a calorie-restricted ketogenic diet. This diet not only reduces the supply of glucose, which fuels cancer cells, but also increases the production of neuroprotective ketone bodies. The combination of DON and the diet had remarkable effects.
Their study in mice, which are the closest models to human glioblastoma, showed that the diet-drug approach effectively killed tumor cells, reversed disease symptoms, improved overall survival, and reduced swelling, bleeding, and inflammation. Importantly, the diet facilitated the delivery of DON to the brain, allowing for a lower dosage to achieve therapeutic effects.
Glioblastoma is known for being particularly resistant to treatment, and current therapies often provide only a limited increase in life expectancy. This new research offers a potential avenue for more effective and less toxic treatment of this aggressive cancer.
Looking ahead, the researchers plan to investigate whether this diet-drug approach can also be effective for other types of cancer. This is because glucose and glutamine, the fuels they targeted in this study, are fundamental to the growth of many cancer types, regardless of their origin in the body.
Source: —Ed Hayward | University Communications | July 2019
