FGFR3 Specific Neutra™ Antibody Products
Product listFGFR3 (Fibroblast growth factor receptor 3, aliases CD333, CEK2, or ACH), belongs to the family of fibroblast growth factor receptors (FGFRs) and shares highly conversed structures with other members, composed of a single transmembrane domain, an acidic region (the acid box), an intracellular domain with two tyrosine kinase domains, a long juxtamembrane domain, and 3 immunoglobulin-like looped domains. The extracellular membrane domain enables FGFR3 to interact with 22 known FGF ligands, extracellular matrix associated proteins, cell adhesion molecules, klotho, FGFR-coreceptors heparan sulfate proteoglycans, as well as multiple non-canonical signaling partners (e.g., N-cadherins or galectins).
Its Gene ID: 2261, UniProtKB ID: P22607, and OMIM ID: 134934.
FGFR3 Signaling Pathways
The primary downstream pathways of FGFR3 are activated by the FRS2, associated with GRB2. RAS guanine exchange factor, GAB1, together with SOS, compose a complex, thus triggering downstream pathways including RAC/JNK, RAS/MEK/MAPK, and PI3K/AKT signaling, subsequently activating STAT1&3 activation, gene translation induction, cell proliferation, and cell survival. On the other hand, the signaling of FGFR3 is also negatively regulated by miRNA-mediated degradation of the receptor and SPRY proteins, which serve as tumor suppressors by negatively regulating the activity of RAS/MAPK.
Fig.1 Downstream molecular interaction network regulated by FGFR3.1, 3
FGFR3 in Diseases
In human lung cancer, it is reported that FGFR3 forms a PRMT5/FGFR3/AKT signaling axis in the epithelial-mesenchymal transition (EMT), regulating the progression and metastasis of tumors. In addition, in heterotopic ossification (HO), it is uncovered that Col2+ lineage cells, which regulate the local inflammatory microenvironment after trauma, influence HO development through the FGFR3-BMPR1a pathway, providing a novel therapeutic target to inhibit acquired HO formation. Besides, as oncogenic fusion genes have been recognized as promising targets in malignancies, FGFR3-TACC3 fusion leads to the constitutive activation of kinase signaling of FGFR3, thereby promoting cell proliferation and progression of tumors.
Fig.2 Schematic diagram describing the role of FGFR3 and lymphatics in acquired HO formation.2, 3
FGFR3-Targeting Antibodies
Since FGFR3 expression alterations are widely reported across a diversity of cancer types, FGFR3-targeting therapies, including antibody therapies, have attracted increasing research interest and there are several therapeutic regimens are being assessed in preclinical and clinical projects. An antibody in phase 1 clinical trials, which binds to FGFR3 with high affinity, has been reported to induce ADCC using in vitro models of multiple myeloma, while it is also well tolerated by patients. For urothelial cell carcinoma, there is another promising FGFR3 monoclonal antibody in clinical development, which is demonstrated to be well tolerated in patients in combination therapy. Moreover, an FGFR3-targeting ADC is reported to lead to a durable complete response in 100% of mice, in an FGFR3-TACC3 fusion-driven lung cancer PDX model.
Creative Biolabs offers different anti-FGFR3 antibody products. These antibodies are recombinantly expressed and could be used for various purposes. Customization of FGFR3-based functional antibodies is also available for you here.
REFERENCES
- Gött, Hanna, and Eberhard Uhl. "FGFR3-TACCs3 fusions and their clinical relevance in human glioblastoma." International Journal of Molecular Sciences 23.15 (2022): 8675.
- Zhang, Dali, et al. "Targeting local lymphatics to ameliorate heterotopic ossification via FGFR3-BMPR1a pathway." Nature communications 12.1 (2021): 4391.
- Distributed under open access license CC BY 4.0, without modification.
