Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer
Abstract Fibroblast growth factors (FGFs) and their receptors regulate numerous cellular processes, such as metabolism and signal transduction, but can also drive tumorigenesis. Specifically, in lung cancer, the overexpression of FGFs, as well as the amplification, mutation and fusion of FGFR genes,...
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| Format: | Article |
| Language: | English |
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BMC
2024-11-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-024-02167-9 |
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| author | Mei Peng Jun Deng Xiangping Li |
| author_facet | Mei Peng Jun Deng Xiangping Li |
| author_sort | Mei Peng |
| collection | DOAJ |
| description | Abstract Fibroblast growth factors (FGFs) and their receptors regulate numerous cellular processes, such as metabolism and signal transduction, but can also drive tumorigenesis. Specifically, in lung cancer, the overexpression of FGFs, as well as the amplification, mutation and fusion of FGFR genes, are closely linked to the initiation, progression and resistance of the disease, suggesting that targeting FGF/FGFR is an attractive therapeutic strategy for lung cancer treatment. Nintedanib, a multitarget tyrosine kinase inhibitor (TKI) used in combination with docetaxel, has shown some success as a second-line therapy for lung cancer. However, clinical trials evaluating other FGFR inhibitors have yielded mixed results, indicating substantial complexity in targeting aberrant FGF/FGFR signaling. In this review, we describe the aberrations in FGF/FGFR signaling in lung cancer and summarize the clinical efficacy of FGFR inhibitors, such as multitarget TKIs, selective FGFR-TKIs and biological agents. We also discuss various challenges associated with FGFR targeting in lung cancer, including precision patient selection, toxicity and resistance. Finally, we provide perspectives on future directions, namely, developing novel FGFR-targeting drugs, such as FGFR degraders and more specific FGFR-TKIs, adopting combination therapy and targeting FGFs. |
| format | Article |
| id | doaj-art-e2ba1edef03f4b95806484c00914b8a9 |
| institution | Kabale University |
| issn | 1476-4598 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-e2ba1edef03f4b95806484c00914b8a92024-11-17T12:13:16ZengBMCMolecular Cancer1476-45982024-11-0123111710.1186/s12943-024-02167-9Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancerMei Peng0Jun Deng1Xiangping Li2Department of Pharmacy, Xiangya Hospital, Central South UniversityDepartment of Pharmacy, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University)Department of Pharmacy, Xiangya Hospital, Central South UniversityAbstract Fibroblast growth factors (FGFs) and their receptors regulate numerous cellular processes, such as metabolism and signal transduction, but can also drive tumorigenesis. Specifically, in lung cancer, the overexpression of FGFs, as well as the amplification, mutation and fusion of FGFR genes, are closely linked to the initiation, progression and resistance of the disease, suggesting that targeting FGF/FGFR is an attractive therapeutic strategy for lung cancer treatment. Nintedanib, a multitarget tyrosine kinase inhibitor (TKI) used in combination with docetaxel, has shown some success as a second-line therapy for lung cancer. However, clinical trials evaluating other FGFR inhibitors have yielded mixed results, indicating substantial complexity in targeting aberrant FGF/FGFR signaling. In this review, we describe the aberrations in FGF/FGFR signaling in lung cancer and summarize the clinical efficacy of FGFR inhibitors, such as multitarget TKIs, selective FGFR-TKIs and biological agents. We also discuss various challenges associated with FGFR targeting in lung cancer, including precision patient selection, toxicity and resistance. Finally, we provide perspectives on future directions, namely, developing novel FGFR-targeting drugs, such as FGFR degraders and more specific FGFR-TKIs, adopting combination therapy and targeting FGFs.https://doi.org/10.1186/s12943-024-02167-9FGFFGFRTargeted drugsLung cancer |
| spellingShingle | Mei Peng Jun Deng Xiangping Li Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer Molecular Cancer FGF FGFR Targeted drugs Lung cancer |
| title | Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer |
| title_full | Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer |
| title_fullStr | Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer |
| title_full_unstemmed | Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer |
| title_short | Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer |
| title_sort | clinical advances and challenges in targeting fgf fgfr signaling in lung cancer |
| topic | FGF FGFR Targeted drugs Lung cancer |
| url | https://doi.org/10.1186/s12943-024-02167-9 |
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