The activation of FGFR1 and TLR4 in cancer cells contributes to inflammatory microenvironment via PI3K/Akt signaling and may make a significant contribution to the progression of human NSCLC.
We have reported previously that, in myeloid and lymphoid malignancies associated with dysregulated fibroblast growth factor receptor 1 (FGFR1) activities, miR-150-5p is down-regulated compared with healthy cells.
However, alterations in FGFRs 1-4, such as amplifications, fusions and mutations, as well as aberrant epigenetic or transcriptional regulation and changes in tumour-stromal interactions in the tumour microenvironment, can lead to the development and/or progression of cancer.
There is substantial evidence for the oncogenic effects of fibroblast growth factor receptor 1 (FGFR1) in many types of cancer, including lung cancer, but the role of this receptor has not been addressed specifically in lung adenocarcinoma.
Using mesenchymal cell lines derived from biopsies of patients who progressed on EGFR TKI as surrogates for persister populations, we performed whole-genome CRISPR screening and identified fibroblast growth factor receptor 1 (FGFR1) as the top target promoting survival of mesenchymal EGFR mutant cancers.
Loss of the intrinsic FGF7/FGF10-type 2 FGF receptor (FGFR2) pathway and gain of the ectopic type 1 FGF receptor (FGFR1) pathway are associated with the progression to malignancy in prostate cancer (PCa) and many other epithelial originating lesions.
FGFR1 has been implicated in numerous cancer types including squamous cell lung cancer, a subset of non-small cell lung cancer with a dismal 5-year survival rate.
Honokiol is a chemical compound that has been proven to be effective against various malignancies and whose analog has been reported to target the mitogen-activated protein kinase family, members of a downstream signaling pathway of FGFR1.
Fibroblast growth factor receptor (FGFR) family has four (FGFR1-4) transmembrane tyrosine kinase receptors expressed on several cell types, and FGFR-1 has been indicated as a potential molecular target in several types of cancer, including oral squamous cell carcinoma (OSCC).
Rogaratinib (BAY 1163877) is a highly potent and selective small-molecule pan-fibroblast growth factor receptor (FGFR) inhibitor (FGFR1-4) for oral application currently being investigated in phase 1 clinical trials for the treatment of cancer.
In 3 representative human cancer cell lines with different mechanisms of FGFR activation tested, SOMCL-085 (20-500 nmol/L) dose-dependently inhibited FGFR1-3 phosphorylation and the phosphorylation of their key downstream effectors PLCγ and Erk.
Fibroblast growth factor receptor-1 (FGFR1) over-expression was broadly found in squamous cancer, where it induced cellular proliferation, differentiation, and metastasis by activating various signaling pathway.