Structural gene rearrangements resulting in gene fusions are frequent events in solid tumours. The identification of certain activating fusions can aid in the diagnosis and effective treatment of patients with tumours harbouring these alterations. Advances in the techniques used to identify fusions have enabled physicians to detect these alterations in the clinic. Targeted therapies directed at constitutively activated oncogenic tyrosine kinases have proven remarkably effective against cancers with fusions involving ALK, ROS1, or PDGFB, and the efficacy of this approach continues to be explored in malignancies with RET, NTRK1/2/3, FGFR1/2/3, and BRAF/CRAF fusions. Nevertheless, prolonged treatment with such tyrosine-kinase inhibitors (TKIs) leads to the development of acquired resistance to therapy. This resistance can be mediated by mutations that alter drug binding, or by the activation of bypass pathways. Second-generation and third-generation TKIs have been developed to overcome resistance, and have variable levels of activity against tumours harbouring individual mutations that confer resistance to first-generation TKIs. The rational sequential administration of different inhibitors is emerging as a new treatment paradigm for patients with tumours that retain continued dependency on the downstream kinase of interest.

导致基因融合的结构基因重排是实体瘤中的常见事件。某些激活融合的识别可以帮助诊断和有效治疗携带这些改变的肿瘤患者。用于识别融合的技术的进步使医生能够在临床上检测到这些变化。针对组成型激活的致癌酪氨酸激酶的靶向治疗已被证明对涉及ALK、ROS1或PDGFB融合的癌症非常有效，并且这种方法在RET、NTRK1/2/3、FGFR1/2/恶性肿瘤中的疗效仍在继续探索。3、以及BRAF/CRAF融合。然而，长期使用此类酪氨酸激酶抑制剂（TKI）治疗会导致获得性治疗耐药性的产生。这种耐药性可以通过改变药物结合的突变或通过激活旁路途径来介导。第二代和第三代 TKI 已被开发用于克服耐药性，并且对具有对第一代 TKI 产生耐药性的个体突变的肿瘤具有不同水平的活性。不同抑制剂的合理序贯给药正在成为持续依赖下游激酶的肿瘤患者的新治疗范例。