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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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What's Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach
Hussein Awada1, Carmelo Gurnari1,2, Zhuoer Xie3
1Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Abstract:
Hypomethylating agents (HMA) such as azacitidine and decitabine are a mainstay in the current management of patients with myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML) as either single agents or in multidrug combinations. Resistance to HMA is not uncommon, and it can result due to several tumor cellular adaptations. Several clinical and genomic factors have been identified as predictors of HMA resistance. However, the management of MDS/AML patients after the failure of HMA remains challenging in the absence of standardized guidelines. Indeed, this is an area of active research with several potential therapeutic agents currently under development, some of which have demonstrated therapeutic potential in early clinical trials, especially in cases with particular mutational characteristics. Here, we review the latest findings and give a rational approach for such a challenging scenario.
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