A clinical-molecular update on azanucleoside-based therapy for the treatment of hematologic cancers.
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Diesch J, Zwick A, Garz AK, Palau A, Buschbeck M, Gotze KS
A clinical-molecular update on azanucleoside-based therapy for the treatment of hematologic cancers.
Clin Epigenetics. 2016 Jun 21;8:71. doi: 10.1186/s13148-016-0237-y. eCollection 2016.
- PubMed ID
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27330573 [View in PubMed]
- Abstract
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The azanucleosides azacitidine and decitabine are currently used for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in patients not only eligible for intensive chemotherapy but are also being explored in other hematologic and solid cancers. Based on their capacity to interfere with the DNA methylation machinery, these drugs are also referred to as hypomethylating agents (HMAs). As DNA methylation contributes to epigenetic regulation, azanucleosides are further considered to be among the first true "epigenetic drugs" that have reached clinical application. However, intriguing new evidence suggests that DNA hypomethylation is not the only mechanism of action for these drugs. This review summarizes the experience from more than 10 years of clinical practice with azanucleosides and discusses their molecular actions, including several not related to DNA methylation. A particular focus is placed on possible causes of primary and acquired resistances to azanucleoside treatment. We highlight current limitations for the success and durability of azanucleoside-based therapy and illustrate that a better understanding of the molecular determinants of drug response holds great potential to overcome resistance.
DrugBank Data that Cites this Article
- Drug Targets
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Drug Target Kind Organism Ph值armacological Action Actions Decitabine DNA Nucleotide Humans YesOther/unknownDetails Decitabine DNA (cytosine-5)-methyltransferase 3A Protein Humans UnknownInhibitorDetails Decitabine DNA (cytosine-5)-methyltransferase 3B Protein Humans UnknownInhibitorDetails - Drug Enzymes
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Drug Enzyme Kind Organism Ph值armacological Action Actions Decitabine Cytidine deaminase Protein Humans NoSubstrateDetails Decitabine Deoxycytidine kinase Protein Humans YesSubstrateDetails Decitabine Nucleoside diphosphokinase (Protein Group) Protein group Humans YesSubstrateDetails Decitabine UMP-CMP kinase Protein Humans YesSubstrateDetails - Drug Reactions
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Reaction Details Details
