Lappi D A
Advanced Targeting Systems, San Diego, CA 92191, USA.
Semin Cancer Biol. 1995 Oct;6(5):279-88. doi: 10.1006/scbi.1995.0036.
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.
成纤维细胞生长因子酪氨酸激酶受体由四个基因编码,但可变剪接可产生100多种可能的蛋白质序列。这些受体在发育中的胚胎中广泛表达,但在成体中表达变得更加局限。由于受体的多样性和大量可能的配体,配体-受体关系很复杂:目前成纤维细胞生长因子家族有九个(可能更多)成员。这种复杂的配体-受体关系通过使用单个配体或受体特异性单克隆抗体为靶向细胞类型创造了许多选择。体内数据表明,FGF受体在肿瘤细胞上表达,可用于靶向肿瘤以抑制其生长。鉴于这种复杂性,有可能在一种或多种肿瘤类型中找到独特的可靶向FGF受体异构体。本文讨论了通过FGF受体将生长抑制剂靶向肿瘤的实例。