Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
Nat Rev Cancer. 2021 May;21(5):313-324. doi: 10.1038/s41568-021-00340-6. Epub 2021 Mar 17.
Focal adhesion kinase (FAK) is both a non-receptor tyrosine kinase and an adaptor protein that primarily regulates adhesion signalling and cell migration, but FAK can also promote cell survival in response to stress. FAK is commonly overexpressed in cancer and is considered a high-value druggable target, with multiple FAK inhibitors currently in development. Evidence suggests that in the clinical setting, FAK targeting will be most effective in combination with other agents so as to reverse failure of chemotherapies or targeted therapies and enhance efficacy of immune-based treatments of solid tumours. Here, we discuss the recent preclinical evidence that implicates FAK in anticancer therapeutic resistance, leading to the view that FAK inhibitors will have their greatest utility as combination therapies in selected patient populations.
黏着斑激酶（FAK）既是一种非受体酪氨酸激酶，也是一种衔接蛋白，主要调节黏附信号和细胞迁移，但 FAK 也可以促进细胞存活以应对应激。FAK 在癌症中普遍过表达，被认为是一个高价值的可成药靶点，目前有多款 FAK 抑制剂正在开发中。有证据表明，在临床环境中，FAK 靶向治疗与其他药物联合使用将最为有效，以逆转化疗或靶向治疗的失败，并增强实体瘤免疫治疗的疗效。在这里，我们讨论了最近的临床前证据，表明 FAK 参与了抗癌治疗耐药性，由此认为 FAK 抑制剂作为联合治疗在特定患者人群中具有最大的应用价值。
