Luo Yuxi, Liu Tianxin, Pei Jinli, Xu Shengnan, Liu Jie, Yu Jinming
Department of Oncology, College of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, 646000, China.
Shandong Provincial Key Laboratory of Precision Oncology, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, Jinan, 250117, China.
Discov Oncol. 2025 Mar 30;16(1):428. doi: 10.1007/s12672-025-02107-z.
Discoidin domain receptor 1 (DDR1) has emerged as a promising therapeutic target in oncology due to its unique role in tumor-stroma interactions and its involvement in key signaling pathways that drive cancer progression. DDR1 is homologous to the transmembrane receptor tyrosine kinase (RTK) family and uniquely requires binding to collagen for its activation. It regulates several cellular processes related to tumor cell proliferation, metabolism, migration, stromal remodeling, and epithelial-mesenchymal transition (EMT), ultimately influencing patient survival. Dysregulation of DDR1 may contribute to cancer progression, neurodegenerative diseases, fibrotic conditions, and atherosclerosis. Moreover, DDR1 has been shown to affect a wide variety of cancers, including lung, breast, stomach, colon, ovarian, and pancreatic cancers, underscoring its potential as a therapeutic target. Various small-molecule tyrosine kinase inhibitors aimed at DDR1 have been developed and have demonstrated significant effectiveness in reducing tumor growth. This review focuses on the structure, function, and mechanism of DDR1, as well as its involvement in cancer progression. Additionally, it examines the development and therapeutic potential of DDR1 inhibitors, offering a comprehensive overview of their application in cancer treatment. By synthesizing current knowledge, this article provides valuable insights to guide future research and innovation in targeting DDR1 for clinical therapeutic advancement.
盘状结构域受体1（DDR1）已成为肿瘤学中一个有前景的治疗靶点，因为它在肿瘤-基质相互作用中具有独特作用，并参与驱动癌症进展的关键信号通路。DDR1与跨膜受体酪氨酸激酶（RTK）家族同源，并且独特地需要与胶原蛋白结合才能被激活。它调节与肿瘤细胞增殖、代谢、迁移、基质重塑和上皮-间质转化（EMT）相关的多个细胞过程，最终影响患者生存。DDR1的失调可能导致癌症进展、神经退行性疾病、纤维化病症和动脉粥样硬化。此外，DDR1已被证明会影响多种癌症，包括肺癌、乳腺癌、胃癌、结肠癌、卵巢癌和胰腺癌，这突出了其作为治疗靶点的潜力。针对DDR1的各种小分子酪氨酸激酶抑制剂已被开发出来，并已证明在减少肿瘤生长方面具有显著效果。本综述重点关注DDR1的结构、功能和机制，以及它在癌症进展中的作用。此外，它还研究了DDR1抑制剂的开发和治疗潜力，全面概述了它们在癌症治疗中的应用。通过综合当前知识，本文提供了有价值的见解，以指导未来针对DDR1进行临床治疗进展的研究和创新。
