Exploring the Cellular and Molecular Mechanism of Discoidin Domain Receptors (DDR1 and DDR2) in Bone Formation, Regeneration, and Its Associated Disease Conditions

Mariadoss, Arokia Vijaya Anand; Wang, Chau-Zen

doi:10.3390/ijms241914895

Cited by 5 publications

(1 citation statement)

References 144 publications

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“…Targeting ECM-related receptors on the cell membrane and cytokines that regulate ECM contribute to enhancing anti-tumor immune response. Integrin and DDR are both important ECM receptors and promising and challenging targets for the treatment of a variety of diseases ( 117 , 118 ). Current research findings indicate that mechanical forces originating from the ECM regulate the stemness and cell cycle of breast cancer cells via the integrin and DDR signaling pathways, thereby promoting tumor proliferation.…”

Section: Emerging Therapeutic Strategies Targeting the Ecmmentioning

confidence: 99%

Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment

Lv,

Fei,

Chen

et al. 2024

Front. Immunol.

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The extracellular matrix (ECM) is a complex three-dimensional structure composed of proteins, glycans, and proteoglycans, constituting a critical component of the tumor microenvironment. Complex interactions among immune cells, extracellular matrix, and tumor cells promote tumor development and metastasis, consequently influencing therapeutic efficacy. Hence, elucidating these interaction mechanisms is pivotal for precision cancer therapy. T lymphocytes are an important component of the immune system, exerting direct anti-tumor effects by attacking tumor cells or releasing lymphokines to enhance immune effects. The ECM significantly influences T cells function and infiltration within the tumor microenvironment, thereby impacting the behavior and biological characteristics of tumor cells. T cells are involved in regulating the synthesis, degradation, and remodeling of the extracellular matrix through the secretion of cytokines and enzymes. As a result, it affects the proliferation and invasive ability of tumor cells as well as the efficacy of immunotherapy. This review discusses the mechanisms underlying T lymphocyte-ECM interactions in the tumor immune microenvironment and their potential application in immunotherapy. It provides novel insights for the development of innovative tumor therapeutic strategies and drug.

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Section: Emerging Therapeutic Strategies Targeting the Ecmmentioning

confidence: 99%

Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment

Lv,

Fei,

Chen

et al. 2024

Front. Immunol.

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Advancement of DDR1 and DDR2 Inhibitors: Therapeutic Potential of Bioactive Compounds, Designing Strategies, and Structure‐Activity Relationship (SAR)

Pal,

Kumaraswamy,

Md. Ashadul

et al. 2024

ChemistrySelect

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DDR1 and DDR2 are nonintegrin collagen receptors in the receptor tyrosine kinase family. Both DDRs bind to various collagen types and perform crucial functions in embryo development. DDRs are different from other receptor tyrosine kinases due to their interaction with extracellular matrix components and unusual activation kinetics. DDR regulates cell migration, survival, proliferation, differentiation, and extracellular matrix remodeling. Dysregulated DDR function is linked to the advancement of several human illnesses, including fibrosis, arthritis, neurodegenerative diseases, and cancer. DDRs play a vital role in disease progression and development. Therefore, the use of DDR inhibitors represents a promising therapeutic strategy, particularly for disorders with limited therapy alternatives. In recent years, DDRs have been regarded as attractive targets for drug development, as evidenced by a significant rise in research in this field. The current review illustrates about recent advancement of small molecules, their designing strategies and structure‐activity relationship. The DDR inhibitors can contain various core structures such as pyrimidine, phthalazine, pyrazole, pyrazine, imidazo[1,2‐a]sspyrazine, quinazoline, and thieno[3,2‐b]pyridin‐7‐yl derivatives. Furthermore, based on the constructive analysis of the published derivatives, we found that the majority of the powerful compounds have a similar scaffold (amide linker, hydrophobic tail, hinge binder with or without spacer). Among the different literature, the most potent compounds 4 (imidazo[1,2‐a]pyrazine), 5 (pyridine), 19 (pyridine), and 24 (quinazoline) displayed potent activity against DDR1 with IC50 values ranging from 2.26 – 4.67 nM, while DDR2 IC50 values ranging from 3.2 – 7.29 nM. This approach will help medicinal chemists to refine and develop novel small molecules targeting DDR1 and DDR2.

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Therapeutic advances of targeting receptor tyrosine kinases in cancer

Tomuleasa,

Tigu,

Munteanu

et al. 2024

Sig Transduct Target Ther

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Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role in cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression of certain RTKs, are critical in creating environments conducive to tumor development. Following their discovery, extensive research has revealed how RTK dysregulation contributes to oncogenesis, with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation, survival and progression. These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer. As a result, RTKs have emerged as primary targets in anticancer therapeutic development. Over the past two decades, this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors (TKIs), now effectively utilized in treating various cancer types. In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer. We explored the various alterations and overexpression of specific receptors across different malignancies, with special attention dedicated to the examination of current RTK inhibitors, highlighting their role as potential targeted therapies. By integrating the latest research findings and clinical evidence, we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.

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Exploring the Cellular and Molecular Mechanism of Discoidin Domain Receptors (DDR1 and DDR2) in Bone Formation, Regeneration, and Its Associated Disease Conditions

Cited by 5 publications

References 144 publications

Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment

Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment

Advancement of DDR1 and DDR2 Inhibitors: Therapeutic Potential of Bioactive Compounds, Designing Strategies, and Structure‐Activity Relationship (SAR)

Therapeutic advances of targeting receptor tyrosine kinases in cancer

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