The Molecular Mechanisms of Resistance to IDH Inhibitors in Acute Myeloid Leukemia.

The Molecular Mechanisms of Resistance to IDH Inhibitors in Acute Myeloid Leukemia.
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DOI:
10.3389/fonc.2022.931462
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发表时间:
2022
影响因子:
4.7
通讯作者:
Chen, Yun
Chen, Yun
中科院分区:
医学3区
文献类型:
--
作者:
Zhuang, Xiaomei;Pei, Han Zhong;Li, Tianwen;Huang, Junbin;Guo, Yao;Zhao, Yuming;Yang, Ming;Zhang, Dengyang;Chang, Zhiguang;Zhang, Qi;Yu, Liuting;He, Chunxiao;Zhang, Liqing;Pan, Yihang;Chen, Chun;Chen, Yun

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异柠檬酸脱氢酶 1/2 (IDH1/2) 的功能获得性突变在急性髓系白血病 (AML) 的发生和进展中发挥着至关重要的作用,这提供了有希望的治疗靶点。两种小分子抑制剂 ivosidenib 和enasidenib 已分别被批准用于治疗 IDH1 和 IDH2 突变型 AML。尽管这些抑制剂在临床上使AML患者受益,但耐药性仍然存在,并成为IDH突变AML靶向治疗的主要问题。许多最新研究已经证明了耐药性的分子机制,为针对突变 IDH1/2 的新型治疗策略提供了理论基础。在这篇综述中,我们讨论了 AML 患者对 ivosidenib 和enasidenib 的耐药机制。
Gain-of-function mutations of isocitrate dehydrogenases 1/2 (IDH1/2) play crucial roles in the development and progression of acute myeloid leukemia (AML), which provide promising therapeutic targets. Two small molecular inhibitors, ivosidenib and enasidenib have been approved for the treatment of IDH1- and IDH2-mutant AML, respectively. Although these inhibitors benefit patients with AML clinically, drug resistance still occurs and have become a major problem for targeted therapies of IDH-mutant AML. A number of up-to-date studies have demonstrated molecular mechanisms of resistance, providing rationales of novel therapeutic strategies targeting mutant IDH1/2. In this review, we discuss mechanisms of resistance to ivosidenib and enasidenib in patients with AML.
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