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白血病化疗中信号通路与激酶抑制剂的最新进展

Recent Advances in Signaling Pathways and Kinase Inhibitors for Leukemia Chemotherapy.

作者信息

Liu Yuying, Yang Zeyu, Zhang Qingqing, Hai Ping, Zheng Yongbiao, Zhang Jie, Pan Xiaoyan

机构信息

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.

NMPA Key Laboratory for Quality Control of Traditional Chinese and Tibetan Medicine, Qinghai Provincial Drug Inspection and Testing Institute, Xining, 810016, China.

出版信息

Curr Med Chem. 2024 Feb 16. doi: 10.2174/0109298673267738231129104216.

Abstract

Leukemia is a malignant clonal disease of hematopoietic stem cells, which accounts for about 3% of the total incidence of tumors and is particularly prevalent among children and adolescents. It mainly includes four types of leukemia, namely ALL, AML, CLL, and CML, which are often aggressive and challenging diseases to treat. Several signaling pathways are dysregulated in almost all types of leukemia, such as JAK, PI3K, and MAPK, and others are dysregulated in specific types of leukemia, like Wnt/β-catenin, Hedgehog, FLT3, Bcr-Abl, and so on. Many efforts have been devoted to developing small molecule inhibitors targeting protein kinases involved in leukemia-related signaling pathways. In this review, we focus on the study of signaling pathways and protein kinases that developed as targets of anti-leukemia drug therapy and report the research progress of relevant small molecule kinase inhibitors over the last five years.

摘要

白血病是一种造血干细胞的恶性克隆性疾病,约占肿瘤总发病率的3%,在儿童和青少年中尤为常见。它主要包括四种类型的白血病,即急性淋巴细胞白血病(ALL)、急性髓系白血病(AML)、慢性淋巴细胞白血病(CLL)和慢性髓系白血病(CML),这些通常都是具有侵袭性且治疗具有挑战性的疾病。几乎在所有类型的白血病中,都有几种信号通路失调,如JAK、PI3K和MAPK,而在特定类型的白血病中,其他信号通路也会失调,如Wnt/β-连环蛋白、Hedgehog、FLT3、Bcr-Abl等。人们致力于开发针对白血病相关信号通路中蛋白激酶的小分子抑制剂。在这篇综述中,我们重点研究作为抗白血病药物治疗靶点的信号通路和蛋白激酶,并报告过去五年相关小分子激酶抑制剂的研究进展。

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