The future of HOXA- expressing leukemias: Menin inhibitor response and resistance.

IF 3.1 3区 医学 Q2 HEMATOLOGY
Current Opinion in Hematology Pub Date : 2024-03-01 Epub Date: 2023-11-23 DOI:10.1097/MOH.0000000000000796
Daniela V Wenge, Scott A Armstrong
{"title":"The future of HOXA- expressing leukemias: Menin inhibitor response and resistance.","authors":"Daniela V Wenge, Scott A Armstrong","doi":"10.1097/MOH.0000000000000796","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>We provide an update on the successes and ongoing challenges of Menin inhibition as a novel approach for the treatment of patients with acute leukemias that express HOXA cluster genes including leukemias with KMT2A -rearrangements, NPM1 mutations or NUP98 -rearrangements. Initial clinical trials show promising response rates in heavily pretreated patients suggesting these inhibitors may have a significant impact on patient outcome. Furthermore, the development of resistance mutations that decrease drug binding affinity, validates Menin as a therapeutic target in human cancers. Therapeutic strategies aiming at overcoming and preventing resistance, are of high clinical relevance.</p><p><strong>Recent findings: </strong>Several Menin inhibitor chemotypes have entered clinical trials. Acquired point mutations have recently been described as a mechanism of resistance towards Menin inhibitors. However, resistance can develop in absence of these mutations. Combination therapies are currently being investigated in preclinical models and in early phase clinical trials.</p><p><strong>Summary: </strong>Given the remarkable overall response rates, shedding light on treatment options for patients whose leukemias develop resistance to Menin inhibitors is an imminent clinical need. Studying the underlying mechanisms to inform clinical decision making, and to potentially prevent the development of resistance is of outmost importance.</p>","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"64-70"},"PeriodicalIF":3.1000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MOH.0000000000000796","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Purpose of review: We provide an update on the successes and ongoing challenges of Menin inhibition as a novel approach for the treatment of patients with acute leukemias that express HOXA cluster genes including leukemias with KMT2A -rearrangements, NPM1 mutations or NUP98 -rearrangements. Initial clinical trials show promising response rates in heavily pretreated patients suggesting these inhibitors may have a significant impact on patient outcome. Furthermore, the development of resistance mutations that decrease drug binding affinity, validates Menin as a therapeutic target in human cancers. Therapeutic strategies aiming at overcoming and preventing resistance, are of high clinical relevance.

Recent findings: Several Menin inhibitor chemotypes have entered clinical trials. Acquired point mutations have recently been described as a mechanism of resistance towards Menin inhibitors. However, resistance can develop in absence of these mutations. Combination therapies are currently being investigated in preclinical models and in early phase clinical trials.

Summary: Given the remarkable overall response rates, shedding light on treatment options for patients whose leukemias develop resistance to Menin inhibitors is an imminent clinical need. Studying the underlying mechanisms to inform clinical decision making, and to potentially prevent the development of resistance is of outmost importance.

表达hoxa的白血病的未来:Menin抑制剂的反应和耐药性。
综述的目的:我们提供了Menin抑制作为一种治疗急性白血病患者HOXA簇基因表达的新方法的最新进展,包括kmt2a重排、NPM1突变或nup98重排的白血病。初步临床试验显示,在大量预处理的患者中,有希望的缓解率表明这些抑制剂可能对患者的预后有重大影响。此外,耐药突变的发展降低了药物结合亲和力,验证了Menin作为人类癌症的治疗靶点。旨在克服和预防耐药性的治疗策略具有很高的临床相关性。最近发现:几种Menin抑制剂化学型已进入临床试验。获得性点突变最近被描述为对Menin抑制剂耐药的机制。然而,在没有这些突变的情况下,耐药性也会产生。目前正在临床前模型和早期临床试验中研究联合疗法。摘要:鉴于显著的总体缓解率,阐明白血病患者对Menin抑制剂产生耐药性的治疗方案是迫在眉睫的临床需求。研究潜在的机制,为临床决策提供信息,并潜在地预防耐药性的发展是至关重要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.60
自引率
3.10%
发文量
78
审稿时长
6-12 weeks
期刊介绍: ​​​​​​​​Current Opinion in Hematology is an easy-to-digest bimonthly journal covering the most interesting and important advances in the field of hematology. Its hand-picked selection of editors ensure the highest quality selection of unbiased review articles on themes from nine key subject areas, including myeloid biology, Vascular biology, hematopoiesis and erythroid system and its diseases.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信