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FGFRFibroblast Growth Factor Receptor
FGFRFresh Gas Flow Rate (anesthesia)
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About one in five patients with advanced UC have a FGFR genetic alteration.4 FGFRs are a family of receptor tyrosine kinases, which can be activated by genetic alterations in a variety of tumor types, and these alterations may lead to increased tumor cell growth and survival.5 A companion diagnostic has also been approved by the FDA to help identify the presence of FGFR alterations in the tumor tissue of patients with metastatic UC.
BALVERSA, a once-daily oral FGFR kinase inhibitor, received accelerated approval based on results from a Phase II trial of 87 patients with disease that had progressed on or after at least one prior chemotherapy and that had at least one of the following genetic alterations: FGFR3 gene mutations (R248C, S249C, G370C, Y373C) or FGFR gene fusions (FGFR3TACC3, FGFR3-BAIAP2L1, FGFR2BICC1, FGFR2-CASP7), as determined by a clinical trial assay performed at a central lab.
FGFRs with genetic aberrations are known to play an important role in the proliferation, survival and migration of cancer cells as well as tumor angiogenesis and drug resistance.
Discovered in-house by Eisai's Tsukuba Research Laboratories, E7090 is an orally available novel tyrosine kinase inhibitor that demonstrates selective inhibitory activity against fibroblast growth factor receptors (FGFR) FGFR1, FGFR2 and FGFR3.
The drug action was not influenced by the blocking of FGFR, PDGFR, and VEGFR function, thus demonstrating that the 2 mechanisms are uncoupled.
The FGFR tyrosine kinase family consists of four kinases: FGFR-1, FGFR-2, FGFR-3 and FGFR-4.
(10) Gene families that could be potential targets include fibroblast growth factor receptor (FGFR), tyrosine kinase KDR (vascular endothelial growth factor receptor 2), and HRAS.
Fibroblast growth factor-like-1 (FGFRL1) is a member of the fibroblast growth factor receptor (FGFR) family [2-6].
Interestingly, many of the enriched pathways are associated with cellular response to extracellular stimuli, organ development, and pathways indirectly associated with cellular metabolism, including the axon guidance pathway (110 gene targets), MAPK signaling cascade (58 gene targets), signaling mediated by FGFR and EGFR (70 and 69 gene targets, resp.), as well as the VEGF pathway (65 gene targets), and insulin-mediated signaling (63 gene targets) (Figure 4) [31, 32].
FGF23 normally binds to FGFR and its coreceptor [alpha]-klotho in order to induce changes in the kidney, the parathyroid gland, and the bone.
Caption: Figure 4: FGFR and AGRT1 mRNA expressions are decreased following Thy1 activation.
FGF-2 plays a critical role in degradation and protection of cartilage depending on its interaction with FGF receptor (FGFR)-1 or FGFR-3, respectively [36].