盘状结构域受体1抑制剂对癌症和炎症相关疾病治疗作用的研究进展

Research progress on discoid domain receptor 1 inhibitors in treating cancers and inflammation associated diseases

盘状结构域受体(DDR)是跨膜受体酪氨酸激酶(RTK)超家族的成员,DDR与RTK的区别在于细胞外结构域中存在盘状蛋白基序,并且可以利用胶原蛋白作为内部配体。目前已鉴定出2种类型的DDR,即DDR1和DDR2,二者具有不同的表达谱和配体特异性。这些DDR在细胞增殖、存活、分化、黏附和基质重塑过程中起着重要作用。DDR与各种癌症、纤维化疾病和动脉粥样硬化等疾病密切相关。DDR1可促进胶原纤维排列,引发免疫排斥。在小鼠模型中,使用DDR1细胞外结构域单克隆抗体、消融DDR1细胞外结构域均可促进肿瘤内T淋巴细胞的渗透,并抑制肿瘤的生长。因此,DDR1被认为是肿瘤新的潜在免疫治疗靶标。本文对DDR1抑制剂对癌症和炎症相关疾病治疗作用的研究进展进行综述。

Discoid domain receptor(DDR)is a member of the transmembrane receptor tyrosine kinase(RTK)superfamily.The difference between DDR and RTK is that there is a discoid motif in the extracellular domain,and collagen can be used as an internal ligand.At present,two types of DDR have been identified,DDR1 and DDR2,which have different expression profiles and ligand specificity.DDR plays an important role in cell proliferation,survival,differentiation,adhesion and matrix remodeling.DDR is closely related to various diseases such as cancer,fibrosis and atherosclerosis.DDR1 can promote the arrangement of collagen fibers and trigger immune rejection.In the mouse model,the use of DDR1 extracellular domain monoclonal antibody and ablation of DDR1 extracellular domain can promote the infiltration of T lymphocytes in the tumor and inhibit the growth of the tumor.Therefore,DDR1 is considered as a new potential molecular target and immune checkpoint.This paper reviews DDR1 inhibitors and their research progress in the treatment of cancer and inflammation associated diseases.