Ketogenic diet in oncology

Scientists from several US research institutions led by Professor Lewis C. Cantley from Cornell University have found in experiments on mice that the so-called ketogenic diet, characterized by a very low carbohydrate and high fat content, increases the effectiveness of a new class of antitumor drugs.

A number of the most common mutations identified in malignant tumor cells are localized in the gene of the enzyme phosphoinositol-3-kinase. This has made this gene a promising target for antitumor drugs and currently more than 20 methods of inhibiting the activity of phosphoinositol-3-kinase are undergoing clinical trials.

However, the results obtained to date are quite contradictory. In some patients, taking such drugs causes a strong increase in blood glucose levels – hyperglycemia. This reaction is often temporary, as the pancreas compensates for it by producing additional insulin. However, in some patients, glucose levels do not normalize, and they are forced to stop taking medications.

The authors drew their attention to the fact that even with the normalization of glucose concentration in the blood of patients, inactivation of phosphoinositol-3-kinase stimulating the growth of cancer cells using experimental drugs does not cause the expected clinical reaction.

In experiments on mice, they demonstrated that an increase in insulin levels reactivated phosphoinositol-3-kinase in a mouse model of a pancreatic tumor receiving the drug Buparlisib, which inhibits the activity of this enzyme. As a result, the drug significantly lost its effectiveness.

This observation prompted researchers to use endocrinological methods for regulating blood glucose and insulin levels. In addition to phosphoinositol-3-kinase inhibitors, they injected animals with antidiabetic drugs metformin or sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Another group of animals was kept on a ketogenic diet.

Metformin, which increases the sensitivity of tissues to insulin, had virtually no effect on glucose and insulin concentrations, as well as on cell signals stimulating tumor growth. SGLT2 inhibitors, which prevent glucose reabsorption in the kidneys and thus enhance its excretion in the urine, reduced the severity of glucose and insulin peaks in response to phosphoinositol-3-kinase inactivation, and also suppressed signals stimulating tumor growth. However, the best results were demonstrated by the ketogenic diet, which has been used in clinical practice for about 40 years to regulate the level of insulin in the blood. According to the authors, its effectiveness of the ketogenic diet is due to the elimination of glycogen reserves, which deprives the body of the ability to release glucose in response to the inactivation of phosphoinositol-3-kinase.

Researchers warn that the ketogenic diet itself not only does not always suppress the growth of malignant tumors, but can also cause harm to the body. Experiments on mouse models have shown that in some types of cancer, in the absence of phosphoinositol-3-kinase inhibitors, the ketogenic diet has virtually no effect on tumors and even contributes to the progression of certain types of leukemia.

In the near future, scientists hope to conduct clinical studies of the effectiveness of the ketogenic diet in combination with phosphoinositol-3-kinase inhibitors approved by the U.S. Food and Drug Administration (FDA) for intravenous administration in patients with breast and endometrial cancer, as well as leukemia and lymphoma.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on Cornell Medicine: Low-carb, high-fat diet may boost targeted cancer therapy.