Sang Yun Beom, Kim Joo-Hang, Kim Chang-Gon, Hong Min Hee, Kim Hye Ryun, Cho Byoung Chul, Lim Sun Min
Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea.
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
Front Oncol. 2022 Mar 3;12:811247. doi: 10.3389/fonc.2022.811247. eCollection 2022.
AXL, along with MER and TYRO3, is a receptor tyrosine kinase from the TAM family. Although AXL itself is not thought to be a potent oncogenic driver, overexpression of AXL is known to trigger tumor cell growth, survival, invasion, metastasis, angiogenesis, epithelial to mesenchymal transition, and immune suppression. Overexpression of AXL is associated with therapy resistance and poor prognosis. Therefore, it is being studied as a marker of prognosis in cancer treatment or as a target in various cancer types. Recently, many preclinical and clinical studies on agents with various mechanisms targeting AXL have been actively conducted. They include small molecule inhibitors, monoclonal antibodies, and antibody-drug conjugates. This article reviewed the fundamental role of AXL in solid tumors, and the development in research of AXL inhibitors in recent years. Emphasis was placed on the function of AXL in acquired therapy resistance in patients with non-small cell lung cancer (NSCLC). Since clinical needs increase in NSCLC patients with acquired resistance after initial therapy, recent research efforts have focused on a combination treatment with AXL inhibitors and tyrosine kinase inhibitors or immunotherapy to overcome resistance. Lastly, we deal with challenges and limitations encountered in the development of AXL inhibitors.
AXL与MER和TYRO3一样，是TAM家族的受体酪氨酸激酶。虽然AXL本身不被认为是一种强大的致癌驱动因子，但已知AXL的过表达会引发肿瘤细胞的生长、存活、侵袭、转移、血管生成、上皮-间质转化和免疫抑制。AXL的过表达与治疗耐药性和不良预后相关。因此，它正在作为癌症治疗预后的标志物或各种癌症类型的靶点进行研究。最近，针对具有多种靶向AXL机制的药物开展了许多临床前和临床研究。这些药物包括小分子抑制剂、单克隆抗体和抗体药物偶联物。本文综述了AXL在实体瘤中的基本作用以及近年来AXL抑制剂的研究进展。重点阐述了AXL在非小细胞肺癌（NSCLC）患者获得性治疗耐药中的作用。由于初始治疗后获得性耐药的NSCLC患者的临床需求增加，最近的研究工作集中在AXL抑制剂与酪氨酸激酶抑制剂或免疫疗法联合治疗以克服耐药性。最后，我们讨论了AXL抑制剂开发中遇到的挑战和局限性。
