This study provides novel epidemiologic data through identification of FGFR1 gene amplification in Chinese NSCLC specimens (particularly squamous) and, importantly, extends the clinical significance of this finding by using multiple FGFR1-amplified squamous lung cancer PDTX models to show tumor stasis or regression effects using a specific FGFR inhibitor (AZD4547).
We identified four cell lines and two newly established primary lung cancer cultures that showed high FGFR1 expression levels, and evaluated the effect of the novel FGFR1 inhibitor ponatinib on cell growth.
Gene amplification of FGFR1 occurs in lung cancer and estrogen receptor (ER)-positive breast cancer, and that of FGFR2 in diffuse-type gastric cancer and triple-negative breast cancer.
A tissue microarray composed of resected lung tumors was submitted to FGFR1 GCN, and mRNA analyses and the results were validated with The Cancer Genome Atlas (TCGA) lung cancer data.
In this study, we deployed RNAi-based functional genomic screens to identify protein kinases controlling the intrinsic sensitivity of FGFR1-dependent lung cancer and head and neck squamous cell cancer (HNSCC) cells to ponatinib, a multikinase FGFR-active inhibitor.
The lung cancer appeared to remain in the stasis phase for 2 years and then burst to stage IV with the amplification of the fibroblast growth factor receptor 1 gene.
These results demonstrate that FGFR1 can mediate adaptive resistance to trametinib and validate a combinatorial approach for treating KRAS-mutant lung cancer.
Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as well as cell growth in lung cancer.
As a consequence, we demonstrate that rational combination therapies resensitize resistant cells to treatment with FGFR inhibitors.<b>Conclusions:</b> We provide evidence for the existence of diverse mechanisms of primary drug resistance in <i>FGFR1</i>-amplified lung cancer and provide a rational strategy to improve FGFR inhibitor therapies by combination treatment.<i></i>.
Here, we identified a FGFR1 inhibitory peptide R1-P2 and investigated its effects on the lung cancer cells growth and angiogenesis <i>in vitro</i> and <i>in vivo</i>.
Histologically diverse lung cancer cell lines were submitted to assays for ponatinib and AZD4547 sensitivity. miRNAs, FGFR1 messenger RNA, gene copy number, and protein expression were detected by real-time quantitative PCR, fluorescence in-situ hybridization, and immunoblotting in 34 lung cancer cell lines.