期刊
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
卷 34, 期 4, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.beha.2021.101325
关键词
Myelodysplastic syndromes; Novel therapies; TP53; NEDD8-activating enzyme; TIM-3; Anti-CD47
类别
Therapeutic options for higher risk myelodysplastic syndromes have been limited, but recent developments in DNA sequencing have led to targeted drug development. Strategies such as disrupting protein ubiquitination, modulating macrophage activity, and blocking immune checkpoints show promise in improving treatment outcomes for high-risk MDS.
Higher risk myelodysplastic syndromes are defined as a subset of disease with higher risk of AML transformation and poor overall survival. For decades, therapeutic options for high-risk MDS have been limited to allogeneic stem cell transplant (the only option for cure but limited to only a handful of patients) or hypomethylating agents, with the goal to alter the natural history of disease, delay progression and improve survival, while addressing cytopenias, transfusion requirements and improving quality of life. Recent developments in DNA sequencing and other technologies have shed significant light into the pathogenesis of MDS and led to rational and targeted drug development across a variety of therapeutic vulnerabilities, including disruption of protein ubiquitination through NAE inhibition, selective modulation of macrophage activity and immune checkpoint inhibition through blockade of TIM-3. This review highlights some of the most promising agents in recent drug development and their therapeutic efficacy in the management of high-risk MDS, and further explores the rationale behind potential combinatorial approaches using an HMA backbone to synergistically improve treatment outcomes.
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