Discoidin domain receptor family (DDR family) (DDR)

The Discoidin Domain Receptor (DDR) family comprises two distinct receptor tyrosine kinases, DDR1 and DDR2, which are unique for being activated by various types of collagen rather than peptide growth factors (NIH, 2021). DDR1 is predominantly expressed in epithelial cells, whereas DDR2 is primarily found in mesenchymal cells like fibroblasts and chondrocytes (Wikipedia, 2024). These receptors serve as key sensors of the extracellular matrix, regulating essential cellular processes including adhesion, proliferation, migration, and matrix remodeling (MDPI, 2021). Dysregulation of DDR signaling is implicated in a wide range of pathologies, most notably in cancer where it drives tumor invasion and metastasis, as well as in organ fibrosis and inflammatory diseases like arthritis (NIH, 2021; ResearchGate, 2021). In oncology, DDR2 mutations have been identified as potential drivers in lung squamous cell carcinoma, while DDR1 overexpression is linked to poor prognosis in several solid tumors (NIH, 2021). While no drugs have been approved specifically for DDR inhibition, several multi-kinase inhibitors such as nilotinib and dasatinib possess potent activity against these receptors, and selective DDR inhibitors are currently under investigation as potential therapeutic agents (NIH, 2021).

Other names

DDRsDiscoidin domain-containing receptorsCD167 familyDDR1DDR2MCK10TKTCAKNTRK4TYRO10Discoidin domain receptor 1Discoidin domain receptor 2

DDR inhibitors bind to the ATP-binding site of the intracellular kinase domain of DDR1 and DDR2, inhibiting their autophosphorylation and blocking downstream signaling cascades such as PI3K/Akt, MAPK/ERK, and STAT pathways, which are normally triggered by collagen binding (NIH, 2021; ResearchGate, 2021).