Only in Titles

Search results for: LY-2874455 Mechanisms: FGF FGFR inhibitor

paperclip

#35814257   2022/06/23 To Up

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 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 and . 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.
Dongcheng Liu, Hongguang Liu, Jiadi Gan, Shinuan Zeng, Fuhua Zhong, Bin Zhang, Zhe Zhang, Siyu Zhang, Lu Jiang, Guangsuo Wang, Yixin Chen, Feng-Ming Spring Kong, Wenfeng Fang, Lingwei Wang

1678 related Products with: LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC.

100ug1 Set1 Set100 μg100 μg100 case

Related Pathways