Discoidin Domain Receptors in Tumor Biology and Immunology: Progression and Challenge

The onset and progression of tumors involve intricate, multifactorial processes. A key component in tumor evolution is the dynamic interaction between cancer cells and the extracellular matrix (ECM). Discoidin Domain Receptors (DDRs), a unique class of collagen-activated receptor tyrosine kinases, serve as critical mediators of cell-ECM communication. Recent studies have uncovered their significant roles in modulating diverse cancer-related processes, including immune responses, cell proliferation, apoptosis, differentiation, metabolic reprogramming, metastasis, and resistance to therapy. This review begins with an overview of the discovery, structural features, and canonical and non-canonical functions of DDRs. It then focuses on the reciprocal regulation between DDRs and collagen in the tumor microenvironment, highlighting how this interplay contributes to cancer progression. Furthermore, we explore the involvement of DDRs in reshaping the tumor immune microenvironment and their influence on various aspects of cancer cell biology. Finally, we summarize the current advances in therapeutic strategies targeting DDRs, offering insights into their potential as biomarkers and drug targets in cancer treatment.