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造血细胞激酶的见解:人类癌症中的致癌因子。

Insights on hematopoietic cell kinase: An oncogenic player in human cancer.

作者信息

Luo Shuyan, Du Shaonan, Tao Mei, Cao Jingyuan, Cheng Peng

机构信息

Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.

Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, 300060 Tianjin, China.

出版信息

Biomed Pharmacother. 2023 Apr;160:114339. doi: 10.1016/j.biopha.2023.114339. Epub 2023 Feb 1.

Abstract

Hematopoietic cell kinase (Hck) is a member of the Src family and is expressed in hematopoietic cells. By regulating multiple signaling pathways, HCK can interact with multiple receptors to regulate signaling events involved in cell adhesion, proliferation, migration, invasion, apoptosis, and angiogenesis. However, aberrant expression of Hck in various hematopoietic cells and solid tumors plays a crucial role in tumor-related properties, including cell proliferation and epithelial-mesenchymal transition. In addition, Hck signaling regulates the function of immune cells such as macrophages, contributing to an immunosuppressive tumor microenvironment. The clinical success of various kinase inhibitors targeting the Src kinase family has validated the efficacy of targeting Src, and therapies with highly selective Hck kinase inhibitors are in clinical trials. This article reviews Hck inhibition as an emerging cancer treatment strategy, focusing on the expressions and functions of Hck in tumors and its impact on the tumor microenvironment. It also explores preclinical and clinical pharmacological strategies for Hck targeting to shed light on Hck-targeted tumor therapy.

摘要

造血细胞激酶(Hck)是Src家族的成员,在造血细胞中表达。通过调节多种信号通路,HCK可与多种受体相互作用,以调节参与细胞黏附、增殖、迁移、侵袭、凋亡和血管生成的信号事件。然而,Hck在各种造血细胞和实体瘤中的异常表达在肿瘤相关特性(包括细胞增殖和上皮-间质转化)中起关键作用。此外,Hck信号传导调节免疫细胞(如巨噬细胞)的功能,促成免疫抑制性肿瘤微环境。各种靶向Src激酶家族的激酶抑制剂在临床上取得的成功证实了靶向Src的有效性,并且高选择性Hck激酶抑制剂疗法正在进行临床试验。本文综述了Hck抑制作为一种新兴的癌症治疗策略,重点关注Hck在肿瘤中的表达和功能及其对肿瘤微环境的影响。它还探讨了针对Hck的临床前和临床药理学策略,以阐明靶向Hck的肿瘤治疗。

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