Tongji University School of Medicine, Shanghai, China.
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Cancer Sci. 2021 Mar;112(3):962-969. doi: 10.1111/cas.14789. Epub 2021 Jan 27.
Discoidin domain receptors (DDR), including DDR1 and DDR2, are special types of the transmembrane receptor tyrosine kinase superfamily. DDR are activated by binding to the triple-helical collagen and, in turn, DDR can activate signal transduction pathways that regulate cell-collagen interactions involved in multiple physiological and pathological processes such as cell proliferation, migration, apoptosis, and cytokine secretion. Recently, DDR have been found to contribute to various diseases, including cancer. In addition, aberrant expressions of DDR have been reported in various human cancers, which indicates that DDR1 and DDR2 could be new targets for cancer treatment. Considerable effort has been made to design DDR inhibitors and several molecules have shown therapeutic effects in pre-clinical models. In this article, we review the recent literature on the role of DDR in cancer progression, the development status of DDR inhibitors, and the clinical potential of targeting DDR in cancer therapies.
Discoidin domain receptors (DDR), including DDR1 and DDR2, are special types of the transmembrane receptor tyrosine kinase superfamily. DDR are activated by binding to the triple-helical collagen and, in turn, DDR can activate signal transduction pathways that regulate cell-collagen interactions involved in multiple physiological and pathological processes such as cell proliferation, migration, apoptosis, and cytokine secretion. Recently, DDR have been found to contribute to various diseases, including cancer. In addition, aberrant expressions of DDR have been reported in various human cancers, which indicates that DDR1 and DDR2 could be new targets for cancer treatment. Considerable effort has been made to design DDR inhibitors and several molecules have shown therapeutic effects in pre-clinical models. In this article, we review the recent literature on the role of DDR in cancer progression, the development status of DDR inhibitors, and the clinical potential of targeting DDR in cancer therapies.
盘状结构域受体(DDR),包括 DDR1 和 DDR2,是跨膜受体酪氨酸激酶超家族的特殊类型。DDR 通过与三螺旋胶原结合而被激活,反过来,DDR 可以激活信号转导通路,调节细胞-胶原相互作用,参与多种生理和病理过程,如细胞增殖、迁移、凋亡和细胞因子分泌。最近,DDR 被发现与多种疾病有关,包括癌症。此外,在各种人类癌症中已经报道了 DDR 的异常表达,这表明 DDR1 和 DDR2 可能成为癌症治疗的新靶点。人们已经做出了相当大的努力来设计 DDR 抑制剂,并且几种分子已经在临床前模型中显示出治疗效果。在本文中,我们回顾了 DDR 在癌症进展中的作用、DDR 抑制剂的发展状况以及在癌症治疗中靶向 DDR 的临床潜力的最新文献。