LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC

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...
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Autor*in:	Dongcheng Liu [verfasserIn] Hongguang Liu [verfasserIn] Jiadi Gan [verfasserIn] Shinuan Zeng [verfasserIn] Fuhua Zhong [verfasserIn] Bin Zhang [verfasserIn] Zhe Zhang [verfasserIn] Siyu Zhang [verfasserIn] Lu Jiang [verfasserIn] Guangsuo Wang [verfasserIn] Yixin Chen [verfasserIn] Feng-Ming Spring Kong [verfasserIn] Wenfeng Fang [verfasserIn] Lingwei Wang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	gefitinib resistance FGF3/4/19/CCND1 amplification NSCLC LY2874455 abemaciclib

Übergeordnetes Werk:	In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphar.2022.918317

Katalog-ID:	DOAJ043954448

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520			\|a 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.
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allfields	10.3389/fphar.2022.918317 doi (DE-627)DOAJ043954448 (DE-599)DOAJ51ac84481c534c0c9e2c578496ce2004 DE-627 ger DE-627 rakwb eng RM1-950 Dongcheng Liu verfasserin aut LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. gefitinib resistance FGF3/4/19/CCND1 amplification NSCLC LY2874455 abemaciclib Therapeutics. Pharmacology Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Hongguang Liu verfasserin aut Jiadi Gan verfasserin aut Shinuan Zeng verfasserin aut Fuhua Zhong verfasserin aut Bin Zhang verfasserin aut Zhe Zhang verfasserin aut Siyu Zhang verfasserin aut Lu Jiang verfasserin aut Guangsuo Wang verfasserin aut Yixin Chen verfasserin aut Feng-Ming Spring Kong verfasserin aut Wenfeng Fang verfasserin aut Lingwei Wang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.918317 kostenfrei https://doaj.org/article/51ac84481c534c0c9e2c578496ce2004 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.918317/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
spelling	10.3389/fphar.2022.918317 doi (DE-627)DOAJ043954448 (DE-599)DOAJ51ac84481c534c0c9e2c578496ce2004 DE-627 ger DE-627 rakwb eng RM1-950 Dongcheng Liu verfasserin aut LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. gefitinib resistance FGF3/4/19/CCND1 amplification NSCLC LY2874455 abemaciclib Therapeutics. Pharmacology Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Hongguang Liu verfasserin aut Jiadi Gan verfasserin aut Shinuan Zeng verfasserin aut Fuhua Zhong verfasserin aut Bin Zhang verfasserin aut Zhe Zhang verfasserin aut Siyu Zhang verfasserin aut Lu Jiang verfasserin aut Guangsuo Wang verfasserin aut Yixin Chen verfasserin aut Feng-Ming Spring Kong verfasserin aut Wenfeng Fang verfasserin aut Lingwei Wang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.918317 kostenfrei https://doaj.org/article/51ac84481c534c0c9e2c578496ce2004 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.918317/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfields_unstemmed	10.3389/fphar.2022.918317 doi (DE-627)DOAJ043954448 (DE-599)DOAJ51ac84481c534c0c9e2c578496ce2004 DE-627 ger DE-627 rakwb eng RM1-950 Dongcheng Liu verfasserin aut LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. gefitinib resistance FGF3/4/19/CCND1 amplification NSCLC LY2874455 abemaciclib Therapeutics. Pharmacology Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Hongguang Liu verfasserin aut Jiadi Gan verfasserin aut Shinuan Zeng verfasserin aut Fuhua Zhong verfasserin aut Bin Zhang verfasserin aut Zhe Zhang verfasserin aut Siyu Zhang verfasserin aut Lu Jiang verfasserin aut Guangsuo Wang verfasserin aut Yixin Chen verfasserin aut Feng-Ming Spring Kong verfasserin aut Wenfeng Fang verfasserin aut Lingwei Wang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.918317 kostenfrei https://doaj.org/article/51ac84481c534c0c9e2c578496ce2004 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.918317/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsGer	10.3389/fphar.2022.918317 doi (DE-627)DOAJ043954448 (DE-599)DOAJ51ac84481c534c0c9e2c578496ce2004 DE-627 ger DE-627 rakwb eng RM1-950 Dongcheng Liu verfasserin aut LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. gefitinib resistance FGF3/4/19/CCND1 amplification NSCLC LY2874455 abemaciclib Therapeutics. Pharmacology Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Hongguang Liu verfasserin aut Jiadi Gan verfasserin aut Shinuan Zeng verfasserin aut Fuhua Zhong verfasserin aut Bin Zhang verfasserin aut Zhe Zhang verfasserin aut Siyu Zhang verfasserin aut Lu Jiang verfasserin aut Guangsuo Wang verfasserin aut Yixin Chen verfasserin aut Feng-Ming Spring Kong verfasserin aut Wenfeng Fang verfasserin aut Lingwei Wang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.918317 kostenfrei https://doaj.org/article/51ac84481c534c0c9e2c578496ce2004 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.918317/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsSound	10.3389/fphar.2022.918317 doi (DE-627)DOAJ043954448 (DE-599)DOAJ51ac84481c534c0c9e2c578496ce2004 DE-627 ger DE-627 rakwb eng RM1-950 Dongcheng Liu verfasserin aut LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. gefitinib resistance FGF3/4/19/CCND1 amplification NSCLC LY2874455 abemaciclib Therapeutics. Pharmacology Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Dongcheng Liu verfasserin aut Hongguang Liu verfasserin aut Jiadi Gan verfasserin aut Shinuan Zeng verfasserin aut Fuhua Zhong verfasserin aut Bin Zhang verfasserin aut Zhe Zhang verfasserin aut Siyu Zhang verfasserin aut Lu Jiang verfasserin aut Guangsuo Wang verfasserin aut Yixin Chen verfasserin aut Feng-Ming Spring Kong verfasserin aut Wenfeng Fang verfasserin aut Lingwei Wang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.918317 kostenfrei https://doaj.org/article/51ac84481c534c0c9e2c578496ce2004 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.918317/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
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topic_facet	gefitinib resistance FGF3/4/19/CCND1 amplification NSCLC LY2874455 abemaciclib Therapeutics. Pharmacology
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container_title	Frontiers in Pharmacology
authorswithroles_txt_mv	Dongcheng Liu @@aut@@ Hongguang Liu @@aut@@ Jiadi Gan @@aut@@ Shinuan Zeng @@aut@@ Fuhua Zhong @@aut@@ Bin Zhang @@aut@@ Zhe Zhang @@aut@@ Siyu Zhang @@aut@@ Lu Jiang @@aut@@ Guangsuo Wang @@aut@@ Yixin Chen @@aut@@ Feng-Ming Spring Kong @@aut@@ Wenfeng Fang @@aut@@ Lingwei Wang @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
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language_de	englisch
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callnumber-first	R - Medicine
author	Dongcheng Liu
spellingShingle	Dongcheng Liu misc RM1-950 misc gefitinib resistance misc FGF3/4/19/CCND1 amplification misc NSCLC misc LY2874455 misc abemaciclib misc Therapeutics. Pharmacology LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC
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topic_title	RM1-950 LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC gefitinib resistance FGF3/4/19/CCND1 amplification NSCLC LY2874455 abemaciclib
topic	misc RM1-950 misc gefitinib resistance misc FGF3/4/19/CCND1 amplification misc NSCLC misc LY2874455 misc abemaciclib misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc gefitinib resistance misc FGF3/4/19/CCND1 amplification misc NSCLC misc LY2874455 misc abemaciclib misc Therapeutics. Pharmacology
topic_browse	misc RM1-950 misc gefitinib resistance misc FGF3/4/19/CCND1 amplification misc NSCLC misc LY2874455 misc abemaciclib misc Therapeutics. Pharmacology
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title	LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC
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title_full	LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC
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title_sort	ly2874455 and abemaciclib reverse fgf3/4/19/ccnd1 amplification mediated gefitinib resistance in nsclc
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title_auth	LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC
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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC
url	https://doi.org/10.3389/fphar.2022.918317 https://doaj.org/article/51ac84481c534c0c9e2c578496ce2004 https://www.frontiersin.org/articles/10.3389/fphar.2022.918317/full https://doaj.org/toc/1663-9812
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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. 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LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC

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