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.

受体酪氨酸激酶 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的异常表达通过生长因子独立性、细胞周期进程、增殖和肿瘤生长、抗细胞凋亡和促进肿瘤转移促进瘤形成。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，促进免疫抑制性肿瘤微环境。各种 MERTK 定向疗法正处于临床前开发阶段，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，重点关注 MERTK 在肿瘤中的表达和功能及其在介导细胞毒性和靶向治疗耐药性以及抑制抗肿瘤免疫方面的作用。此外，我们回顾了针对 MERTK 的临床前和临床药理学策略。