Awada Hussein, Gurnari Carmelo, Xie Zhuoer, Bewersdorf Jan Philipp, Zeidan Amer M
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
Cancers (Basel). 2023 Apr 12;15(8):2248. doi: 10.3390/cancers15082248.
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.
阿扎胞苷和地西他滨等去甲基化药物（HMA）是目前治疗骨髓增生异常综合征/肿瘤（MDS）和急性髓系白血病（AML）患者的主要药物，可单独使用或与多种药物联合使用。对HMA耐药并不罕见，它可能是由多种肿瘤细胞适应性变化导致的。一些临床和基因组因素已被确定为HMA耐药的预测指标。然而，在缺乏标准化指南的情况下，HMA治疗失败后MDS/AML患者的管理仍然具有挑战性。事实上，这是一个正在积极研究的领域，目前有几种潜在的治疗药物正在研发中，其中一些在早期临床试验中已显示出治疗潜力，特别是在具有特定突变特征的病例中。在此，我们综述了最新研究结果，并针对这种具有挑战性的情况给出了合理的应对方法。
