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000305684 1001_ $$00009-0009-1522-211X$$aWenger, Valentin$$b0
000305684 245__ $$aDNA methyltransferase inhibitors in hematological malignancies and solid tumors.
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000305684 520__ $$aEpigenetic modifications such as DNA methylation play a fundamental role in oncogenesis and the progression of neoplasms neoplasias. DNA methyltransferase inhibitors (DNMTi) constitute a family of therapeutic agents that impede the methylation at the 5-position on cytosine nucleotides, thereby modulating the epigenetic regulation of tumor suppressor genes, oncogenes, and other key regulatory genes. The first-generation DNMTi azacitidine and decitabine have demonstrated substantial efficacy in the treatment of medically non-fit, older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy (IC), by virtue of their favorable safety profile. Despite these clinical achievements, however, single-agent DNMTi treatment has faced challenges such as limited, non-durable response rates and remissions as well as the emergence of secondary resistance. These limitations have driven broad efforts to identify more effective, dual treatment combinations, such as now attained with the DNMTi-BCL-2 (B-cell lymphoma 2) inhibitor combination. This review aims to provide a comprehensive overview and analysis of the pivotal role of DNMTi in both mono- and combination therapies for myeloid malignancies over the last 40 years, while also exploring their potential applicability in lymphoid malignancies. Additionally, this review assesses the therapeutic potential of DNMTi in the management of solid tumors. Through these discussions, we intend to enhance the understanding of the mechanistic and therapeutic implications of DNMTi across a diverse array of malignancies.
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000305684 650_7 $$2Other$$adifferentiation
000305684 650_7 $$2Other$$aepigenetic therapy
000305684 650_7 $$2Other$$ahypomethylating agents
000305684 650_7 $$2Other$$aretinoic acid
000305684 650_7 $$2Other$$avenetoclax
000305684 7001_ $$aGarcia-Manero, Guillermo$$b1
000305684 7001_ $$0P:(DE-HGF)0$$aZeiser, Robert$$b2
000305684 7001_ $$00000-0003-1186-1650$$aLübbert, Michael$$b3
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