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- W2912465046 abstract "Introduction: There is evidence of the association of DNA methylation alterations with cancer development and progression.Areas covered: This review will briefly discuss the basis of epigenetics and the clinical results of first-generation DNA methyltransferase inhibitors (DNMTi) in myelodysplastic syndrome (MDS) and solid tumors, as well as the limited clinical information on second-generation DNMTi.Expert opinion: Azacitidine and decitabine are FDA-approved for the treatment of MDS but show limited activity against solid tumors despite inducing gene promoter demethylation, gene reactivation, and global demethylation. Nevertheless, no data consistently shows that the response to these drugs is associated with any DNA methylation marker. It is key to increase clinical exploratory trials with existing and novel demethylating agents incorporating ‘omics’ technologies to identify DNA methylation ‘drivers’ or ‘`patterns’ unique to specific malignancies and then proceed to clinical trials in highly selected patients. Ongoing studies with novel DNMTi would inform whether these agents overcome the pharmacological limitations of current DNMTi and improve their efficacy. Interestingly, solid preclinical data indicate that acquired DNA hypermethylation impedes PD-1 blockade-mediated T-cell rejuvenation and this phenomenon can be reverted with decitabine; moreover, this drug synergizes CTLA-4 blockade in vivo. This promising research avenue is now clinically being tested." @default.
- W2912465046 created "2019-02-21" @default.
- W2912465046 creator A5048475618 @default.
- W2912465046 creator A5070192692 @default.
- W2912465046 date "2019-01-02" @default.
- W2912465046 modified "2023-10-15" @default.
- W2912465046 title "Emerging DNA methylation inhibitors for cancer therapy: challenges and prospects" @default.
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- W2912465046 doi "https://doi.org/10.1080/23808993.2019.1571906" @default.
- W2912465046 hasPublicationYear "2019" @default.
- W2912465046 type Work @default.