Tumor targeting through fibroblast growth factor receptors.
Fibroblast growth factor tyrosine kinase receptors are encoded by four genes, but alternate splicing can result in more than 100 possible protein sequences. The receptors have widespread expression in the developing embryo, but the expression becomes more restricted in the adult. The ligand-receptor relationship is complex, due to the diversity of the receptors and the large number of possible ligands: there are now nine (and probably more) members of the fibroblast growth factor family. This complicated ligand-receptor relationship creates many options to target cell types through the use of individual ligands or receptor-specific monoclonal antibodies. In-vivo data demonstrate that FGF receptors are expressed on tumor cells and can be used to target tumors for growth inhibition. Given the complexity, it is possible that a unique targetable FGF receptor isoform can be found in one or more tumor types. Examples of the targeting of growth inhibition agents to tumors through FGF receptors are discussed.
Lappi
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Advanced Targeting Systems, San Diego, CA 92191, USA.
D000595:Amino Acid Sequence; D000818:Animals; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000628:therapy*; D010940:Plant Proteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000627:therapeutic use; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D005346:Fibroblast Growth Factors; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D000922:Immunotoxins; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins; D011509:Proteoglycans; D020794:Receptor Protein-Tyrosine Kinases; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins