MERTK in cancer therapy: Targeting the receptor tyrosine kinase in tumor cells and the immune system.
MERTK in cancer therapy: Targeting the receptor tyrosine kinase in tumor cells and the immune system.
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MerTK在癌症治疗中的作用：靶向肿瘤细胞和免疫系统中的受体酪氨酸激酶。
DOI：
10.1016/j.pharmthera.2020.107577
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发表时间：
2020-09
影响因子：
13.5
通讯作者：
Graham, Douglas K.
中科院分区：
文献类型：
--
作者：
Huelse, Justus M.;Fridlyand, Diana M.;Earp, Shelton;DeRyckere, Deborah;Graham, Douglas K.
酪氨酸激酶受体MERTK在许多人类恶性肿瘤中异常表达，是癌症治疗的新靶点。MERTK的生理作用包括调节组织稳态和修复、先天免疫控制和血小板聚集。然而，在广泛的液体和固体恶性肿瘤中，异常表达通过生长因子独立性、细胞周期进展、增殖和肿瘤生长、细胞凋亡抵抗和促进肿瘤转移来促进肿瘤形成。此外，MERTK信号通过诱导抗炎细胞因子谱和调节PD-1轴，以及调节巨噬细胞、髓源性抑制细胞、自然杀伤细胞和T细胞功能，有助于免疫抑制肿瘤微环境。各种mertk导向的疗法正在临床前开发中，临床试验正在进行中。在这篇综述中，我们讨论了MERTK抑制作为一种新兴的癌症治疗策略，重点讨论了MERTK在肿瘤中的表达和功能，以及它在介导对细胞毒性和靶向治疗的抗性以及抑制抗肿瘤免疫中的作用。此外，我们回顾了针对MERTK的临床前和临床药理策略。
The receptor tyrosine kinase MERTK is aberrantly expressed in numerous human malignancies, and is a novel target in cancer therapeutics. Physiologic roles of MERTK include regulation of tissue homeostasis and repair, innate immune control, and platelet aggregation. However, aberrant expression in a wide range of liquid and solid malignancies promotes neoplasia via growth factor independence, cell cycle progression, proliferation and tumor growth, resistance to apoptosis, and promotion of tumor metastases. Additionally, MERTK signaling contributes to an immunosuppressive tumor microenvironment via induction of an anti-inflammatory cytokine profile and regulation of the PD-1 axis, as well as regulation of macrophage, myeloid-derived suppressor cell, natural killer cell and T cell functions. Various MERTK-directed therapies are in preclinical development, and clinical trials are underway. In this review we discuss MERTK inhibition as an emerging strategy for cancer therapy, focusing on MERTK expression and function in neoplasia and its role in mediating resistance to cytotoxic and targeted therapies as well as in suppressing anti-tumor immunity. Additionally, we review preclinical and clinical pharmacological strategies to target MERTK.
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PD-1和PD-L1检查点信号传导抑制癌症免疫疗法：机制，组合和临床结果。
影响因子：
5.6
作者：
Alsaab HO;Sau S;Alzhrani R;Tatiparti K;Bhise K;Kashaw SK;Iyer AK
通讯作者：
Iyer AK
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11.2
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影响因子：
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通讯作者：
Jabbour, Elias