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REVIEW

Oral DNA Demethylating Agents and Epigenetic Targeting in Adult T-Cell Leukemia/Lymphoma

Yuta Yamamoto1,2, Hiroshi Ureshino1,2,*, Shinya Kimura1,2
1 Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
2 Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Saga, Japan
* Corresponding Author: Hiroshi Ureshino. Email: email
(This article belongs to the Special Issue: Molecular Targeting Therapy for Anticancer Treatment)

Oncology Research https://doi.org/10.32604/or.2026.084740

Received 28 April 2026; Accepted 16 June 2026; Published online 03 July 2026

Abstract

DNA methylation plays a critical role in gene regulation and is frequently dysregulated in hematological malignancies such as myelodysplastic syndromes and acute myeloid leukemia. DNA demethylating agents have therefore emerged as important therapeutic options. However, conventional DNA demethylating agents require parenteral administration, which limits their long-term use and patient convenience. In this review, we aim to provide an overview of recent advances in the development of orally available DNA demethylating agents and discuss their therapeutic applications in hematological malignancies. Orally available DNA demethylating agents, such as CC-486 (oral azacitidine) and ASTX727 (a fixed-dose combination of oral decitabine and the cytidine deaminase inhibitor cedazuridine), have been developed to overcome these limitations and enable sustained drug exposure. In addition, OR-2100, a novel oral prodrug of decitabine, has been shown to exhibit improved pharmacokinetic properties and reduced hematologic toxicity in preclinical studies. These findings suggest that orally available DNA demethylating agents may expand therapeutic options, particularly for hematological malignancies such as adult T-cell leukemia/lymphoma.

Keywords

DNA methylation; DNA demethylating agents; epigenetic therapy; OR-2100; adult T-cell leukemia/lymphoma

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