Department of Oncology, Laboratory of Structural Biology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Clinical Anatomy and Reproductive Medicine Application Institute, Department of Histology and Embryology, Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, University of South China, Hengyang, 421001, China.
J Hematol Oncol. 2021 Feb 10;14(1):23. doi: 10.1186/s13045-021-01040-2.
Fibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concern. Here, we review the mechanisms of FGFR-TKI resistance in cancer, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. In addition, we summarize strategies to overcome resistance, including developing covalent inhibitors, developing dual-target inhibitors, adopting combination therapy, and targeting lysosomes, which will facilitate the transition to precision medicine and individualized treatment.
成纤维细胞生长因子受体（FGFRs）在促进癌细胞的增殖、分化和迁移中发挥着关键作用。酪氨酸激酶抑制剂（TKI）对 FGFRs 的失活在肿瘤靶向治疗中取得了巨大成功。然而，FGFR-TKI 的耐药性已成为人们关注的焦点。本文综述了 FGFR-TKI 耐药性的机制，包括看门基因突变、替代信号通路激活、溶酶体介导的 TKI 隔离和基因融合。此外，还总结了克服耐药性的策略，包括开发共价抑制剂、开发双靶抑制剂、采用联合治疗和靶向溶酶体，这将有助于向精准医学和个体化治疗的转变。
