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- Publisher Website: 10.3389/fphar.2022.918317
- Scopus: eid_2-s2.0-85133842125
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Article: LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC
Title | LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC |
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Authors | |
Keywords | abemaciclib FGF3/4/19/CCND1 amplification gefitinib resistance LY2874455 NSCLC |
Issue Date | 23-Jun-2022 |
Publisher | Frontiers Media |
Citation | Frontiers in Pharmacology, 2022, v. 13 How to Cite? |
Abstract | Non-small cell lung carcinoma (NSCLC) patients who initially received tyrosine kinase inhibitor (TKI) therapy often acquired resistance via multiple complex mechanisms. The amplification of FGF3/4/19/CCND1 on chromosome 11q13 was found in many cancers with TKI resistance. However, the role of these amplifications in TKI-resistant NSCLC remains uncovered. Here, we generated the FGF3/4/19/CCND1 amplification model in the NSCLC cell lines PC-9 and HCC827. Upregulation of FGF3/4/19/CCND1 strongly promoted cell proliferation and gefitinib resistance in NSCLC cells. To find out the potential therapeutic strategies, we screened the combination of inhibitors against the FGF/FGFR signaling pathway and the CCND1/CDK4 complex and revealed that gefitinib combined with LY2874455 and abemaciclib exhibited the most effective inhibition of resistance in vitro and in vivo. Mechanistically, FGFs/CCND1 activated the MAPK pathway, which was abolished by the combination drugs. Our study provides a rationale for clinical testing of dual targeting FGFR and CCND1 with LY2874455 and abemaciclib in NSCLC patients who harbored FGF3/4/19/CCND1 amplification. |
Persistent Identifier | http://hdl.handle.net/10722/343923 |
ISSN | 2023 Impact Factor: 4.4 2023 SCImago Journal Rankings: 1.066 |
DC Field | Value | Language |
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dc.contributor.author | Liu, Dongcheng | - |
dc.contributor.author | Liu, Hongguang | - |
dc.contributor.author | Gan, Jiadi | - |
dc.contributor.author | Zeng, Shinuan | - |
dc.contributor.author | Zhong, Fuhua | - |
dc.contributor.author | Zhang, Bin | - |
dc.contributor.author | Zhang, Zhe | - |
dc.contributor.author | Zhang, Siyu | - |
dc.contributor.author | Jiang, Lu | - |
dc.contributor.author | Wang, Guangsuo | - |
dc.contributor.author | Chen, Yixin | - |
dc.contributor.author | Kong, Feng-Ming Spring | - |
dc.contributor.author | Fang, Wenfeng | - |
dc.contributor.author | Wang, Lingwei | - |
dc.date.accessioned | 2024-06-18T03:42:51Z | - |
dc.date.available | 2024-06-18T03:42:51Z | - |
dc.date.issued | 2022-06-23 | - |
dc.identifier.citation | Frontiers in Pharmacology, 2022, v. 13 | - |
dc.identifier.issn | 1663-9812 | - |
dc.identifier.uri | http://hdl.handle.net/10722/343923 | - |
dc.description.abstract | <p>Non-small cell lung carcinoma (NSCLC) patients who initially received tyrosine kinase inhibitor (TKI) therapy often acquired resistance <em>via</em> multiple complex mechanisms. The amplification of FGF3/4/19/CCND1 on chromosome 11q13 was found in many cancers with TKI resistance. However, the role of these amplifications in TKI-resistant NSCLC remains uncovered. Here, we generated the FGF3/4/19/CCND1 amplification model in the NSCLC cell lines PC-9 and HCC827. Upregulation of FGF3/4/19/CCND1 strongly promoted cell proliferation and gefitinib resistance in NSCLC cells. To find out the potential therapeutic strategies, we screened the combination of inhibitors against the FGF/FGFR signaling pathway and the CCND1/CDK4 complex and revealed that gefitinib combined with LY2874455 and abemaciclib exhibited the most effective inhibition of resistance <em>in vitro</em> and <em>in vivo</em>. Mechanistically, FGFs/CCND1 activated the MAPK pathway, which was abolished by the combination drugs. Our study provides a rationale for clinical testing of dual targeting FGFR and CCND1 with LY2874455 and abemaciclib in NSCLC patients who harbored FGF3/4/19/CCND1 amplification.<br></p> | - |
dc.language | eng | - |
dc.publisher | Frontiers Media | - |
dc.relation.ispartof | Frontiers in Pharmacology | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | abemaciclib | - |
dc.subject | FGF3/4/19/CCND1 amplification | - |
dc.subject | gefitinib resistance | - |
dc.subject | LY2874455 | - |
dc.subject | NSCLC | - |
dc.title | LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC | - |
dc.type | Article | - |
dc.identifier.doi | 10.3389/fphar.2022.918317 | - |
dc.identifier.scopus | eid_2-s2.0-85133842125 | - |
dc.identifier.volume | 13 | - |
dc.identifier.eissn | 1663-9812 | - |
dc.identifier.issnl | 1663-9812 | - |