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用于急性髓系白血病治疗的激酶抑制剂联合疗法

Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.

作者信息

Takahashi Shinichiro

机构信息

Division of Laboratory Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan.

出版信息

Hematol Rep. 2023 May 24;15(2):331-346. doi: 10.3390/hematolrep15020035.

Abstract

Targeting kinase activity is considered to be an attractive therapeutic strategy to overcome acute myeloid leukemia (AML) since aberrant activation of the kinase pathway plays a pivotal role in leukemogenesis through abnormal cell proliferation and differentiation block. Although clinical trials for kinase modulators as single agents remain scarce, combination therapies are an area of therapeutic interest. In this review, the author summarizes attractive kinase pathways for therapeutic targets and the combination strategies for these pathways. Specifically, the review focuses on combination therapies targeting the FLT3 pathways, as well as PI3K/AKT/mTOR, CDK and CHK1 pathways. From a literature review, combination therapies with the kinase inhibitors appear more promising than monotherapies with individual agents. Therefore, the development of efficient combination therapies with kinase inhibitors may result in effective therapeutic strategies for AML.

摘要

靶向激酶活性被认为是克服急性髓系白血病(AML)的一种有吸引力的治疗策略,因为激酶途径的异常激活通过异常的细胞增殖和分化阻滞在白血病发生过程中起关键作用。尽管作为单一药物的激酶调节剂的临床试验仍然很少,但联合疗法是一个具有治疗意义的领域。在这篇综述中,作者总结了有吸引力的作为治疗靶点的激酶途径以及这些途径的联合策略。具体而言,该综述重点关注靶向FLT3途径以及PI3K/AKT/mTOR、CDK和CHK1途径的联合疗法。从文献综述来看,激酶抑制剂联合疗法似乎比单一药物单药治疗更有前景。因此,开发有效的激酶抑制剂联合疗法可能会产生针对AML的有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7c3/10297912/36dd73dea39d/hematolrep-15-00035-g001.jpg

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