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FGFR-TKI resistance in cancer: current status and perspectives.

ABSTRACT: 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.

SUBMITTER: Yue S

PROVIDER: S-EPMC7876795 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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FGFR-TKI resistance in cancer: current status and perspectives.

Yue Sitong S Li Yukun Y Chen Xiaojuan X Wang Juan J Li Meixiang M Chen Yongheng Y Wu Daichao D

Journal of hematology & oncology 20210210 1

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 a ...[more]

PMID: 33568192

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