Discoidin domain receptors (DDRs), including DDR1 and DDR2, are a unique class of receptor tyrosine kinases (RTKs) activated by collagens at the cell-matrix boundary interface. The peculiar mode of activation makes DDRs as key cellular sensors of microenvironmental changes, with a critical role in all physiological and pathological processes governed by collagen remodeling. DDRs are widely expressed in fetal and adult tissues, and experimental and clinical evidence has shown that their expression is deregulated in cancer. Strong findings supporting the role of collagens in tumor progression and metastasis have led to renewed interest in DDRs. However, despite an increasing number of studies, DDR biology remains poorly understood, particularly the less studied DDR2, whose involvement in cancer progression mechanisms is undoubted. Thus, the understanding of a wider range of DDR2 functions and related molecular mechanisms is expected. To date, several lines of evidence support DDR2 as a promising target in cancer therapy. Its involvement in key functions in the tumor microenvironment makes DDR2 inhibition particularly attractive to achieve simultaneous targeting of tumor and stromal cells, and tumor regression, which is beneficial for improving the response to different types of anti-cancer therapies, including chemo- and immunotherapy. This review summarizes current research on DDR2, focusing on its role in cancer progression through its involvement in tumor and stromal cell functions, and discusses findings that support the rationale for future development of direct clinical strategies targeting DDR2.

盘状结构域受体 (DDR)，包括 DDR1 和 DDR2，是一类独特的受体酪氨酸激酶 (RTK)，由细胞-基质边界界面处的胶原蛋白激活。独特的激活模式使 DDR 成为微环境变化的关键细胞传感器，在胶原蛋白重塑控制的所有生理和病理过程中发挥关键作用。 DDR 在胎儿和成人组织中广泛表达，实验和临床证据表明它们的表达在癌症中失调。支持胶原蛋白在肿瘤进展和转移中的作用的有力研究结果引起了人们对 DDR 的新兴趣。然而，尽管研究数量不断增加，但人们对 DDR 生物学仍然知之甚少，尤其是研究较少的 DDR2，其与癌症进展机制的参与是毋庸置疑的。因此，人们期望了解更广泛的 DDR2 功能和相关分子机制。迄今为止，多项证据支持 DDR2 作为癌症治疗的一个有前景的靶点。它参与肿瘤微环境的关键功能，使得DDR2抑制对于实现同时靶向肿瘤和基质细胞以及肿瘤消退特别有吸引力，这有利于改善对不同类型抗癌疗法（包括化疗和免疫疗法）的反应。本综述总结了 DDR2 目前的研究，重点关注其通过参与肿瘤和基质细胞功能在癌症进展中的作用，并讨论了支持未来开发针对 DDR2 的直接临床策略的基本原理的研究结果。