Gay Carl M, Balaji Kavitha, Byers Lauren Averett
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Br J Cancer. 2017 Feb 14;116(4):415-423. doi: 10.1038/bjc.2016.428. Epub 2017 Jan 10.
The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers. In the context of malignancy, evidence suggests that AXL overexpression drives wide-ranging processes, including epithelial to mesenchymal transition, tumour angiogenesis, resistance to chemotherapeutic and targeted agents, and decreased antitumor immune response. As a result, AXL is an attractive candidate not only as a prognostic biomarker in malignancy but also as a target for anticancer therapies. Several AXL inhibitors are currently in preclinical and clinical development. This article reviews the structure, regulation, and function of AXL; the role of AXL in the tumour microenvironment; the development of AXL as a therapeutic target; and areas of ongoing and future investigation.
受体酪氨酸激酶AXL通过其配体生长停滞特异性蛋白6与磷脂酰丝氨酸之间的复杂相互作用而被激活，它调节多种重要的细胞过程，包括增殖、存活、迁移和免疫反应。虽然AXL本身并未被认为是致癌驱动因子，但它是受体酪氨酸激酶TYRO3、AXL和MERTK家族的成员，在包括急性髓系白血病、非小细胞肺癌、胃和结肠腺癌以及乳腺癌和前列腺癌在内的多种血液系统和实体恶性肿瘤中均有过表达。在恶性肿瘤的背景下，有证据表明AXL的过表达驱动了广泛的过程，包括上皮-间质转化、肿瘤血管生成、对化疗药物和靶向药物的耐药性以及抗肿瘤免疫反应的降低。因此，AXL不仅是恶性肿瘤中一个有吸引力的预后生物标志物，也是抗癌治疗的一个靶点。目前有几种AXL抑制剂正处于临床前和临床开发阶段。本文综述了AXL的结构、调节和功能；AXL在肿瘤微环境中的作用；AXL作为治疗靶点的开发；以及正在进行和未来研究的领域。
