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Review
. 2023 Aug 8:10:1222908.
doi: 10.3389/fnut.2023.1222908. eCollection 2023.

Current knowledges in pharmaconutrition: " Ketogenics" in pediatric gliomas

Nicola Cecchi  1 , Roberta Romanelli  1 , Flavia Ricevuti  1 , Marianna Amitrano  2 , Maria Grazia Carbone  1 , Michele Dinardo  1 , Ernesto Burgio  3
Affiliations
Review

Current knowledges in pharmaconutrition: " Ketogenics" in pediatric gliomas

Nicola Cecchi et al. Front Nutr. .

Abstract

Brain tumors account for 20-25% of pediatric cancers. The most frequent type of brain tumor is Glioma from grade I to grade IV according to the rate of malignancy. Current treatments for gliomas use chemotherapy, radiotherapy, tyrosine kinase inhibitors, monoclonal antibodies and surgery, but each of the treatment strategies has several serious side effects. Therefore, to improve treatment efficacy, it is necessary to tailor therapies to patient and tumor characteristics, using appropriate molecular targets. An increasingly popular strategy is pharmaconutrition, which combines a tailored pharmacological treatment with a diet designed to synergize the effects of drugs. In this review we deal in the molecular mechanisms, the epigenetic effects and modulation of the oxidative stress pathway of ketogenic diets, that underlie its possible role, in the treatment of infantile gliomas, as a complementary approach to conventional cancer therapy.

Keywords: brain cancer; epigenetic; glioma; ketogenic diet; pediatrics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Nutritional characteristics of ketogenic dietary therapies.
Figure 2
Figure 2
The biochemistry of the ketogenic diet. Hepatocytes must use all available oxalate for gluconeogenesis, causing a reduction of the TCA cycle.
Figure 3
Figure 3
Illustration of cell behavior during ketogenic diet. (A) in normal cells fed KD, lower level of glucose increases the level of ketone bodies as a result of the increase in free fatty acids, thus increasing the level of acetyl-CoA in mitochondria for production of ATP. (B) in cancer cells fed KD, it reduces glycolysis. In addition, mitochondria may be dysfunctional and the cells are unable to produce ATP; therefore, KD prevents cancer cell proliferation.
Figure 4
Figure 4
DNA methylation regulates Carbohydrate metabolic pathways in cancer cells. DNA hypermethylation of the DERL3 promoter by DNMT1 and DNMT3b lead to the upregulation of GLUT1 in cancer cells. This drives to an increased glucose uptake and a high rate of glycolysis in tumor cells.
Figure 5
Figure 5
Ketotherapy and epigenetic modifications. KDs could act as epigenetic drugs by sensitizing radiotherapy-resistant patients. Radiosensitivity would be promoted by some epigenetic modifications by KDs (40).
Figure 6
Figure 6
Biosynthetic pathways of b-hydroxybutyrate and b-hydroxybutyryl-CoA. Also depicted are the three ketone bodies: b-hydroxybutyrate, acetoacetate, and acetone.
Figure 7
Figure 7
Role of ROS in signal transduction. PI3K/AKT/mTOR signaling activates two major signaling pathways: Ras-MAPK, which leads to cell proliferation, and PI3K-Akt-eNOS, determines cell survival. In cancer cells, a high concentration of ROS activates the survival pathway and inactivates the PTEN pathway to avoid apoptosis.
Figure 8
Figure 8
Modulation of oxidative stress. How KD differentially affects metabolism of normal and malignant brain cells.
See this image and copyright information in PMC

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