靶向功能隐匿的 TAM 受体家族的治疗方法。
Therapeutic targeting of the functionally elusive TAM receptor family.
机构信息
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Oncology, University of Oxford, Oxford, UK.
出版信息
Nat Rev Drug Discov. 2024 Mar;23(3):201-217. doi: 10.1038/s41573-023-00846-8. Epub 2023 Dec 13.
The TAM receptor family of TYRO3, AXL and MERTK regulates tissue and immune homeostasis. Aberrant TAM receptor signalling has been linked to a range of diseases, including cancer, fibrosis and viral infections. Specifically, the dysregulation of TAM receptors can enhance tumour growth and metastasis due to their involvement in multiple oncogenic pathways. For example, TAM receptors have been implicated in the epithelial-mesenchymal transition, maintaining the stem cell phenotype, immune modulation, proliferation, angiogenesis and resistance to conventional and targeted therapies. Therapeutically, multiple TAM receptor inhibitors are in preclinical and clinical development for cancers and other indications, with those targeting AXL being the most clinically advanced. Although there has been notable clinical advancement in recent years, challenges persist. This Review aims to provide both biological and clinical insights into the current therapeutic landscape of TAM receptor inhibitors, and evaluates their potential for the treatment of cancer and non-malignant diseases.
TYRO3、AXL 和 MERTK 组成的 TAM 受体家族调节组织和免疫稳态。异常的 TAM 受体信号与一系列疾病有关，包括癌症、纤维化和病毒感染。具体来说，由于 TAM 受体参与多种致癌途径，其失调会增强肿瘤生长和转移。例如，TAM 受体参与上皮-间充质转化、维持干细胞表型、免疫调节、增殖、血管生成以及对传统和靶向治疗的耐药性。在治疗方面，多种 TAM 受体抑制剂正在进行癌症和其他适应症的临床前和临床开发，其中靶向 AXL 的抑制剂处于最先进的临床阶段。尽管近年来取得了显著的临床进展，但挑战依然存在。本综述旨在为 TAM 受体抑制剂的治疗现状提供生物学和临床方面的见解，并评估其在癌症和非恶性疾病治疗中的潜力。
Zotero 插件