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Fibroblast Growth Factors FGFs - Biotech, Pharma and Life Science Channel

23:14 EST 19th February 2018 | BioPortfolio

The family of fibroblast growth factors (FGFs) regulates a plethora of developmental processes, including brain patterning, branching morphogenesis and limb development.

Quite a number of FGF-R agonists are in development or even marketed in a range of different indications of tissue repair:

Cancer: FGF/FGFR signalling is important in tumour angiogenesis but studies in the last few years have uncovered increasing evidence that FGFRs are driving oncogenes in certain cancers and act in a cell autonomous fashion to maintain the malignant properties of tumour cells. These observations make FGFRs increasingly attractive as targets for therapeutic intervention in cancer. There is a range of therapeutic strategies currently employed or in development to antagonise de-regulated FGFRs including antibodies and small molecule tyrosine kinase inhibitors.

Cardiovascular Diseases: Fibroblast growth factor-2 (FGF-2 has been shown over the years to exert acute and direct pro-survival effects, irrespectively of whether it is administered before, during or after an ischemic insult to the heart. FGF-2 is also a potent angiogenic protein and a crucial agent for the proliferation, expansion, and survival of several cell types including those with stem cell properties. Human clinical trials have pointed to a good safety record for this protein.

Wound Healing:  Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF, but FGF is shown to have a role in tissue repair, so may lead to novel treatments.

Dental and Bone Tissue Repair: The role of growth factors (GF) in bone repair is widely recognised, particularly for bone morphogenetic proteins (BMPs) and fibroblast growth factor (FGF). GF are usually stored in the extracellular matrix (ECM), but after injury are actively released by ECM, cells and platelets.

Source; Pharmacol Ther. 2010 Jan;125(1):105-17. (De-regulated FGF receptors as therapeutic targets in cancer)

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Medical and Biotech [MESH] Definitions

A fibroblast growth factor receptor with specificity for FIBROBLAST GROWTH FACTORS; HEPARAN SULFATE PROTEOGLYCAN; and NEURONAL CELL ADHESION MOLECULES. Several variants of the receptor exist due to multiple ALTERNATIVE SPLICING of its mRNA. Fibroblast growth factor receptor 1 is a tyrosine kinase that transmits signals through the MAP KINASE SIGNALING SYSTEM.

A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.

A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in APERT SYNDROME.

The most divergent of the known fibroblast growth factor receptors. It does not contain an intracellular TYROSINE KINASE domain and has been shown to interact with FIBROBLAST GROWTH FACTOR 2. Fibroblast growth factor receptor 5 is found primarily in skeletal tissue.

These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic FIBROBLAST GROWTH FACTORS but have different amino acid sequences.

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