Discoidin domain receptor 1 as a potent therapeutic target in solid tumors
Shaheen Bibi,
Weihong Zeng,
Peiyi Zheng,
Seyed Majid Mousavi Mehmandousti,
Tengchuan Jin
Affiliations
Shaheen Bibi
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Anhui, China
Weihong Zeng
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Anhui, China
Peiyi Zheng
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Anhui, China
Seyed Majid Mousavi Mehmandousti
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Anhui, China
Tengchuan Jin
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Anhui, China; Laboratory of Structural Immunology, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, Anhui, China; Biomedical Sciences and Health Laboratory of Anhui Province, University of Science & Technology of China, Anhui, China; Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Anhui, China; Correspondence
Despite significant discoveries in basic cancer research and improvements in treatment options and clinical outcomes, cancer remains a major public health concern worldwide. Today, the main focus of cancer research is the signaling pathways that are crucial for cell survival, cell proliferation, and cell migration. The aberrant expression of proteins involved in these signaling pathways often leads to abnormal cell growth, cell metastasis, and invasion of healthy tissues. One such protein is discoidin domain receptor 1 (DDR1) which belongs to the family of receptor tyrosine kinases (RTKs) and is activated upon collagen binding, as a result, downstream signaling pathways are stimulated which are responsible for cell survival, cell growth, adhesion, extracellular matrix remodeling, and cell migration. DDR1 is found to have abnormally elevated expression in various solid tumors, implying a critical role in cancer progression. Traditional cancer treatment involves the use of cytotoxic drugs, chemotherapy, radiotherapy, and surgery, which do not provide long-term survival and often result in cancer recurrence. Numerous small-molecule kinase inhibitors have been synthesized against RTKs including DDR1 and have been highly efficacious in tumor reduction. More recently, targeting the DDR1 extracellular domain (ECD) has garnered much attention from researchers, as inhibiting the DDR1-collagen binding has been attributed to maximizing the likelihood of the combined cytotoxic effect of both immune cells and targeted drugs. This review focuses on the structure, function, activation, and signaling partners of DDR1, its role in different solid tumors, and finally discusses about designing more DDR1 non-kinase inhibitors as promising therapeutic strategies against DDR1-driven tumors.
