Ketotherapy as an epigenetic modifier in cancer
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Ketotherapy as an epigenetic modifier in cancer Borja Bandera-Merchan 1 & Hatim Boughanem 2 & Ana B. Crujeiras 3,4 & Manuel Macias-Gonzalez 1,4 Francisco J. Tinahones 1,4
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# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Epigenetic alterations in cancer play a variety of roles. Aberrant DNA methylation, as one of the epigenetic mechanisms, has been widely studied in both tumor and liquid biopsies and provide a useful bench mark for treatment response in cancer. Recently, several studies have reported an association between the type of diet and epigenetic modifications. Whereby there is a growing interest in finding the “anti-cancer diet formula”, if such a thing exists. In this sense, ketogenic diets (KD) have reported potentially beneficial effects, which were able to prevent malignancies and decrease tumor growth. Some studies have even shown increased survival in cancer patients, reduced side effects of cytotoxic treatments, and intensified efficacy of cancer therapies. Although the biological mechanisms of KD are not well understood, it has been reported that KD may affect DNA methylation by modulating the expression of crucial genes involved in tumor survival and proliferation. However, there are many considerations to take into account to use ketotherapy in cancer, such as epigenetic mark, type of cancer, immunological and metabolic state or microbiota profile. In this review, we argue about ketotherapy as a potential strategy to consider as coadjuvant of cancer therapy. We will focus on mainly epigenetic mechanisms and dietary approach that could be included in the current clinical practice guidelines. Keywords Cancer . Epigenetic . Ketogenic diet . Ketone bodies . DNA methylation . Kethotherapy . Epigenetic drugs
1 Introduction: cancer and epigenetics Epigenetic modifications are heritable and dynamic chemical modifications in DNA/RNA and histones, which ultimately modulate transcriptional activity. Multiple microenvironmental factors can induce such reversible chemical modifications in nucleic acids. Consequently, the epigenomic mark is the result of a complex regulatory circuit between
* Manuel Macias-Gonzalez [email protected] 1
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Málaga, Spain
2
Biomedical Research Institute of Malaga (IBIMA). Faculty of Science, University of Malaga, 29010 Málaga, Spain
3
Epigenomics in Endocrinology and Nutrition Group, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), 15706 Santiago de Compostela, Spain
4
CIBEROBN (CIBER in Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain
genetic and environmental factors on multiple levels [1]. So far, DNA methylation is considered the most studied epigenetic mechanism. DNA methylation occurs at the carbon 5 position of cytosine in a cytosine-guanine pair (CpG dinucleotide). A methyl group is covalently attached to
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