FGFR-TKI resistance in cancer: current status and perspectives
Open Access
- 10 February 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Hematology & Oncology
- Vol. 14 (1), 1-14
- https://doi.org/10.1186/s13045-021-01040-2
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.Keywords
Funding Information
- National Natural Science Foundation of China (81974074 and 81570537)
- Outstanding youth project of Hunan Education Department (19B475)
- Open Project of State Local Joint Engineering Laboratory for Anticancer Drugs (KAYW-FK-20-01)
- Scientific Research Foundation of the University of South China (190XQD016)
This publication has 126 references indexed in Scilit:
- Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancersApoptosis, 2013
- A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loopOncogenesis, 2013
- High-Throughput Mutation Profiling of Primary and Metastatic Endometrial Cancers Identifies KRAS, FGFR2 and PIK3CA to Be Frequently MutatedPLOS ONE, 2012
- Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancersCell Death & Disease, 2012
- Oncogene Mutation Profiling of Pediatric Solid Tumors Reveals Significant Subsets of Embryonal Rhabdomyosarcoma and Neuroblastoma with Mutated Genes in Growth Signaling PathwaysClinical Cancer Research, 2012
- Increased expression of histone demethylase JHDM1D under nutrient starvation suppresses tumor growth via down-regulating angiogenesisProceedings of the National Academy of Sciences of the United States of America, 2011
- ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drugHaematologica, 2009
- Fibroblast Growth Factor (FGF) and FGF Receptor-Mediated Autocrine Signaling in Non-Small-Cell Lung Cancer CellsMolecular Pharmacology, 2008
- Drug-sensitiveFGFR2mutations in endometrial carcinomaProceedings of the National Academy of Sciences of the United States of America, 2008
- A Molecular Brake in the Kinase Hinge Region Regulates the Activity of Receptor Tyrosine KinasesMolecular Cell, 2007