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Targeting DNA Hypomethylation in Malignancy by Epigenetic Therapies

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Human Cell Transformation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1164))

Abstract

DNA methylation is a chemically reversible epigenetic modification that regulates the chromatin structure and gene expression, and thereby takes part in various cellular processes like embryogenesis, genomic imprinting, X-chromosome inactivation, and genome stability. Alterations in the normal methylation levels of DNA may contribute to the development of pathological conditions like cancer. Even though both hypo- and hypermethylation-mediated abnormalities are prevalent in the cancer genome, the field of cancer epigenetics has been more focused on targeting hypermethylation. As a result, DNA hypomethylation-mediated abnormalities remained relatively less explored, and currently, there are no approved drugs that can be clinically used to target hypomethylation. Understanding the precise role of DNA hypomethylation is not only crucial from a mechanistic point of view but also for the development of pharmacological agents that can reverse the hypomethylated state of the DNA. This chapter focuses on the causes and impact of DNA hypomethylation in the development of cancer and describes the possible ways to pharmacologically target it, especially by using a naturally occurring physiologic agent S-adenosylmethionine (SAM).

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Acknowledgements

This work was supported by grants from the Canadian Institutes for Health Research (MOP 130410 and PJT-156225) to SAR. NM is the recipient of a Ruth and Alex Dworkin Fellowship from the Faculty of Medicine, McGill University.

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The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Medicine, McGill University Health Centre, Montréal, QC, Canada

    Niaz Mahmood & Shafaat A. Rabbani

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  1. Niaz Mahmood
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  2. Shafaat A. Rabbani
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Correspondence to Shafaat A. Rabbani .

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  1. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Johng S. Rhim

  2. Georgetown University Medical Center, Washington, DC, USA

    Anatoly Dritschilo

  3. Department of Medicine, McGill University Health Centre, Montréal, QC, Canada

    Richard Kremer

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Mahmood, N., Rabbani, S.A. (2019). Targeting DNA Hypomethylation in Malignancy by Epigenetic Therapies. In: Rhim, J., Dritschilo, A., Kremer, R. (eds) Human Cell Transformation. Advances in Experimental Medicine and Biology, vol 1164. Springer, Cham. https://doi.org/10.1007/978-3-030-22254-3_14

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