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Published on: September 30, 2016
Emerging strategies and translational advancements of DDR1 in oncology
Yuxi Luo1,2, Tianxin Liu2,3, Jinli Pei2
1Department of Oncology, College of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, 646000, China.
Abstract:
Discoidin domain receptor 1 (DDR1) has emerged as a promising therapeutic target in oncology due to its unique role in tumor-stroma interactions and its involvement in key signaling pathways that drive cancer progression. DDR1 is homologous to the transmembrane receptor tyrosine kinase (RTK) family and uniquely requires binding to collagen for its activation. It regulates several cellular processes related to tumor cell proliferation, metabolism, migration, stromal remodeling, and epithelial-mesenchymal transition (EMT), ultimately influencing patient survival. Dysregulation of DDR1 may contribute to cancer progression, neurodegenerative diseases, fibrotic conditions, and atherosclerosis. Moreover, DDR1 has been shown to affect a wide variety of cancers, including lung, breast, stomach, colon, ovarian, and pancreatic cancers, underscoring its potential as a therapeutic target. Various small-molecule tyrosine kinase inhibitors aimed at DDR1 have been developed and have demonstrated significant effectiveness in reducing tumor growth. This review focuses on the structure, function, and mechanism of DDR1, as well as its involvement in cancer progression. Additionally, it examines the development and therapeutic potential of DDR1 inhibitors, offering a comprehensive overview of their application in cancer treatment. By synthesizing current knowledge, this article provides valuable insights to guide future research and innovation in targeting DDR1 for clinical therapeutic advancement.
Insights
Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase crucial for cancer progression. Targeting DDR1 with inhibitors shows promise for reducing tumor growth and advancing cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase implicated in tumor-stroma interactions and cancer progression.
- DDR1 activation by collagen regulates cellular processes including proliferation, migration, and epithelial-mesenchymal transition (EMT).
- Dysregulation of DDR1 is linked to various cancers and other diseases like fibrosis and atherosclerosis.
Purpose of the Study:
- To review the structure, function, and mechanism of DDR1.
- To explore DDR1's involvement in cancer progression across multiple cancer types.
- To examine the development and therapeutic potential of DDR1 inhibitors in oncology.
Main Methods:
- Literature review synthesizing current research on DDR1.
- Analysis of DDR1's role in signaling pathways and cellular processes.
- Evaluation of preclinical and clinical data on DDR1 inhibitors.
Main Results:
- DDR1 plays a significant role in tumor cell proliferation, metabolism, migration, stromal remodeling, and EMT.
- DDR1 dysregulation is associated with lung, breast, stomach, colon, ovarian, and pancreatic cancers.
- Small-molecule DDR1 inhibitors have demonstrated effectiveness in reducing tumor growth.
Conclusions:
- DDR1 is a validated therapeutic target in oncology due to its multifaceted role in cancer.
- DDR1 inhibitors represent a promising strategy for cancer treatment.
- Further research into DDR1 targeting is crucial for clinical therapeutic advancement.
