Venetoclax在急性髓系白血病中的作用。

IF 2.5 4区 医学 Q3 ONCOLOGY Recent patents on anti-cancer drug discovery Pub Date : 2023-01-01 DOI:10.2174/1574892817666220429105338
Romeo G Mihăilă
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引用次数: 0

摘要

背景:在过去十年中,由于基因编辑和描述性和功能基因组学的进步,用于治疗急性髓性白血病的治疗武器库取得了实质性进展。目的:分析维妥乐治疗急性髓系白血病的疗效和安全性。方法:使用检索词“acute myeloid leukemia”和“venetoclax”以及该领域发表的新专利,检索2021年5月5日前在PubMed和Web of Science上发表的文章,进行小型综述。结果:BCL-2抑制剂在单药治疗中对急性髓系白血病细胞有活性,但其疗效部分受到限制,因为它们不靶向其他抗凋亡蛋白和venetoclax诱导其他抗凋亡分子的过表达。以venetoclax为基础的联合治疗(包括与低甲基化药物联合治疗)能够改善老年急性髓性白血病患者的预后,包括缓解率和总生存率。与venetoclax联合使用的其他药物包括:FLT3抑制剂、IDH2抑制剂、奇达胺、依鲁替尼、拉帕替尼、米韦布雷布、雷公藤甲素、代谢抑制剂、核苷类似物和经典化疗药物。分析了维托霉霉耐药的机理、克服途径以及维托霉霉的不良反应。结论:不适应和老年急性髓性白血病患者的管理应个性化,并应评估患者和疾病特异性因素,这些因素对他们的护理至关重要。对他们中的许多人来说,包括venetoclax的组合是一个越来越好的选择。
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Venetoclax in Acute Myeloid Leukemia.

Background: Substantial progress in the therapeutic arsenal used to treat acute myeloid leukemia became possible in the last decade, as a result of advances in gene editing and descriptive and functional genomics.

Objective: The aim of this study is to analyze the efficacy and safety of venetoclax in the treatment of acute myeloid leukemia.

Methods: A mini-review was achieved using the articles published in PubMed and Web of Science in the last year, prior to 05.05.2021, which were searched using the terms "acute myeloid leukemia" and "venetoclax" and the new patents published in this field.

Results: BCL-2 inhibitors administered in monotherapy are active against acute myeloid leukemia cells, but their efficacy is partially limited because they do not target other antiapoptotic proteins and venetoclax induced overexpression of the other antiapoptotic molecules. Venetoclax-based combinations (including those with hypomethylating agents) were able to improve outcomes for older patients with acute myeloid leukemia, including both remission rates and overall survival. Other drugs used in combination with venetoclax include: FLT3 inhibitors, IDH2 inhibitors, chidamide, ibrutinib, lapatinib, mivebresib, triptolide, metabolic inhibitors, nucleoside analogs, and classical chemotherapeutics. Both the mechanisms of venetoclax resistance and the ways to overcome it, as well as the adverse effects of venetoclax are analyzed.

Conclusion: The management of unfit and older patients with acute myeloid leukemia should be personalized and be the result of evaluating patient- and disease-specific factors that are essential to their care. Combinations that include venetoclax are an increasingly well-documented option for many of them.

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来源期刊
CiteScore
4.50
自引率
7.10%
发文量
55
审稿时长
3 months
期刊介绍: Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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