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Epigenetic Regulator, Re-emerging Antimetabolites with Novel Mechanism of Action (Azacitidine and Decitabine): Clinical Pharmacology and Therapeutic Results

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Chemotherapy for Leukemia

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Abstract

Hypomethylating agents, such as azacitidine (AZA) and decitabine (DAC), are antimetabolites with a very unique mechanism of action as epigenetic regulator. After being incorporated into the DNA, these inhibit the enzyme, DNA methyltransferase, resulting in the hypomethylation of DNA, and change the expression of many genes. AZA is also incorporated into RNA, which will also disturb protein synthesis. AZA and DAC are now used to treat some hematological neoplasms, especially for the treatment of myelodysplastic syndromes (MDS). After several clinical trials, AZA became the first agent shown to prolong overall survival for higher-risk MDS. Treatment with AZA or DAC is also showed to improve cytopenia in MDS and to provide longer leukemia-free survival than other treatment. Although the precise mechanism is not revealed yet, AZA is widely used to treat MDS and, recently, acute leukemia of the elderly. Oral AZA is also under clinical development.

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Authors and Affiliations

  1. Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Shinya Sato & Yasushi Miyazaki

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  1. Shinya Sato
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  2. Yasushi Miyazaki
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Correspondence to Yasushi Miyazaki .

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Editors and Affiliations

  1. University of Fukui, Fukui, Japan

    Takanori Ueda

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Sato, S., Miyazaki, Y. (2017). Epigenetic Regulator, Re-emerging Antimetabolites with Novel Mechanism of Action (Azacitidine and Decitabine): Clinical Pharmacology and Therapeutic Results. In: Ueda, T. (eds) Chemotherapy for Leukemia. Springer, Singapore. https://doi.org/10.1007/978-981-10-3332-2_19

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  • DOI: https://doi.org/10.1007/978-981-10-3332-2_19

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  • Online ISBN: 978-981-10-3332-2

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