Discoidin Domain Receptor 1 as Modifier of Collagen in Tumor Extracellular Matrix: Recent Advances and Therapeutic Possibilities

Purpose of Review Immune exclusion and dormancy in cancer pose hurdles in successful cancer therapy. The review details the role played by discoidin domain receptor 1 (DDR1) in accumulation of collagen in the extracellular matrix of cancer. DDR1 contributes to immune exclusion and dormancy by specific alignment of collagen in extracellular matrix. Therapeutic targeting of DDR1 is thus evaluated as a viable option in cancer treatment. Recent Findings For many years, researchers believed that the intracellular kinase domain of DDR1 is the major contributing factor in cancer development and progression. The extracellular domain (ECD) of DDR1 that holds the collagen binding pocket is responsible for collagen alignment at the cancer matrix. The ECD-DDR1 alone determines the specific alignment of collagen that decides the various determinants of cancer that includes dormancy, immune exclusion, and metastasis. Summary Many cancer types attain increased expression of collagen contributing to density and high-order alignment that can be associated to poor prognosis. Discoidin domain receptors (DDRs) are collagen binding receptors which on activation initiate various cellular responses. Overexpression of DDR1 in cancer cells is correlated to lesser infiltration of immune cells into tumor and also linked to dormant state of tumors.