March 2022
Adrienne C. Scheck, Nelofer Syed
Abstract
Malignant brain tumors are devastating despite aggressive treatments, including surgical resection, chemotherapy, and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately 18 months, and increased survival requires the design of new therapeutic modalities, especially those that enhance currently available treatments.
One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacologic means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD).
Preclinical work has shown that the KD does indeed reduce tumor growth in vivo, and it reduces angiogenesis, inflammation, peritumoral edema, migration, and invasion. Furthermore, the KD can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival.
Additional studies in vitro have indicated that increasing ketones in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of radiation.
The pluripotent effects exhibited by ketogenic therapy may be due, in part, to epigenetic changes. The main ketone, β-hydroxybutyrate, is a class 1 histone deacetylase inhibitor, and we have shown that the expression of a number of microRNAs is altered in tumors of mice fed a KD compared to standard diet. Thus, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas.
Keywords: glioma, ketogenic diet, metabolism, mouse model, clinical medicine, therapy, epigenetics
