The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development

SIMPLE SUMMARY: The tumor microenvironment plays an important role in tumor development and metastasis. Collagens are major components of the extracellular matrix and can influence tumor development and metastasis by activating discoidin domain receptors (DDRs). This work shows the different roles of DDRs in various cancers and highlights the complexity of anti-DDR therapies in cancer treatment. ABSTRACT: The tumor microenvironment is a complex structure composed of the extracellular matrix (ECM) and nontumoral cells (notably cancer-associated fibroblasts (CAFs) and immune cells). Collagens are the main components of the ECM and they are extensively remodeled during tumor progression. Some collagens are ligands for the discoidin domain receptor tyrosine kinases, DDR1 and DDR2. DDRs are involved in different stages of tumor development and metastasis formation. In this review, we present the different roles of DDRs in these processes and discuss controversial findings. We conclude by describing emerging DDR inhibitory strategies, which could be used as new alternatives for the treatment of patients.