FGFR-TKI resistance in cancer: current status and perspectives
Open accessAbstract
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.
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Dysregulated FGF-FGFR signaling participates in cancer development by activating MAPK, PI3K, and PLC-γ pathways.
“Dysregulated fibroblast growth factor-fibroblast growth factor receptor (FGF-FGFR) signaling participates in cancer development by activating MAPK, PI3K, and PLC-γ pathways [232, 233].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [232]
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References 129 · Cited by 145
- Authors
- Yue, S., Li, Y., Chen, X., Wang, J., Li, M., Chen, Y., & Wu, D.
- Affiliations
- Central South University (CN)
- University of South China (CN)
- Corresponding author
- Chen, Yongheng
- Wu, Daichao
- Venue
- Journal of Hematology & Oncology
- Published
- 2021-02-10
- Volume
- 14
- Issue
- 1
- Pages
- 23-23
- ISSN
- 1756-8722 (ISSN-L)
- PMC
- PMC7876795
- OpenAlex
- W3126629350
- Cited by
- 145
- References
- 129
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 38 · 2023: 22 · 2022: 33 · 2021: 10
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Hematology & Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- 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)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- fibroblast growth factor receptor, tyrosine kinase inhibitors, drug resistance, gatekeeper mutation, alternative signaling pathways, covalent inhibitors, dual inhibitors, combination therapy, lysosomal targeting, precision medicine
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Mutation, Neoplasms, Protein-Tyrosine Kinases, Signal Transduction, Receptors, Fibroblast Growth Factor, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, Molecular Targeted Therapy
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