Tumor metabolism, the ketogenic diet and beta-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy
Author(s)
Woolf, EC
Syed, N
Scheck, AC
Type
Journal Article
Abstract
Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. 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 pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD). The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet 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 such as β-hydroxybutyrate (βHB) in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.
Date Issued
2016-11-16
Date Acceptance
2016-10-31
Citation
Frontiers in Molecular Neuroscience, 2016, 9
ISSN
1662-5099
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Molecular Neuroscience
Volume
9
Copyright Statement
© 2016 Woolf, Syed and Scheck. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000387817000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neurosciences & Neurology
glioblastoma
glioma
cancer
metabolism
ketogenicdiet
beta-hydroxybutyrate
ketones
POLYUNSATURATED FATTY-ACIDS
HYPOXIA-INDUCIBLE-FACTOR
CANCER-CELL METABOLISM
MOUSE XENOGRAFT MODEL
KETONE-BODIES
ENERGY-METABOLISM
PROSTATE-CANCER
CARBOHYDRATE RESTRICTION
GLIOBLASTOMA-MULTIFORME
CALORIC RESTRICTION
Publication Status
Published
Article Number
ARTN 122