DDR1 and DDR2: a review on signaling pathway and small molecule inhibitors as an anticancer agent

Matada, Gurubasavaraja Swamy Purawarga; Das, Arka; Dhiwar, Prasad Sanjay; Ghara, Abhishek

doi:10.1007/s00044-020-02694-2

Cited by 20 publications

(10 citation statements)

References 96 publications

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“…DDR1 and DDR2 dysregulation has been linked to multiple forms of cancer. Many studies have shown that elevated DDR expression levels and/or mutations can be found in a number of cancer cell lines as well as primary tumor tissues including lung [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ], pancreas [ 48 ], prostate [ 49 ], breast [ 50 , 51 ], brain [ 52 , 53 ], ovary [ 54 , 55 ], liver [ 56 ], and others [ 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. DDR1 was found to be a prognostic marker for non-small-cell lung carcinoma (NSCLC) patients.…”

Section: Role Of Ddr In Cancermentioning

confidence: 99%

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

Elkamhawy

Nada

et al. 2021

IJMS

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Discoidin domain receptor (DDR) is a collagen-activated receptor tyrosine kinase that plays critical roles in regulating essential cellular processes such as morphogenesis, differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. As a result, DDR dysregulation has been attributed to a variety of human cancer disorders, for instance, non-small-cell lung carcinoma (NSCLC), ovarian cancer, glioblastoma, and breast cancer, in addition to some inflammatory and neurodegenerative disorders. Since the target identification in the early 1990s to date, a lot of efforts have been devoted to the development of DDR inhibitors. From a medicinal chemistry perspective, we attempted to reveal the progress in the development of the most promising DDR1 and DDR2 small molecule inhibitors covering their design approaches, structure-activity relationship (SAR), biological activity, and selectivity.

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Section: Role Of Ddr In Cancermentioning

confidence: 99%

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

Elkamhawy

Nada

et al. 2021

IJMS

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“…Thus, dysregulation of DDR1 may lead to metastatic cancer progressions. Gather evidence con rmed overexpression of DDR1 in invasive tumors that showed enhanced migration and invasion in cancer cells [21][22][23][24]. Upregulation of DDR1 in NSCLC tissues indicated that increased DDR1 expression might be involved in the development and progression of NSCLC.…”

Section: Discussionmentioning

confidence: 96%

The influence of discoidin domain receptor 1 expression on angiogenic factors: VEGF-A and FGF-2 in non-small cell lung cancer

et al. 2023

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“…As a major ECM component, collagen regulates various steps of cancer progression including growth, invasion, and metastasis, partly through activation of its canonical receptor integrin to regulate cytoskeleton organization and cell motility (5)(6)(7). Recently, discoidin domain receptor tyrosine kinase 2 (DDR2), a non-typical collagen receptor that is dysregulated in various cancer types, has emerged as a key signaling molecule in carcinogenesis (8,9). Collagen binding to DDR2 activates its tyrosine kinase activity to initiate canonical pathways such as ERK1/2 and PI3 kinase signaling (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, discoidin domain receptor tyrosine kinase 2 (DDR2), a non-typical collagen receptor that is dysregulated in various cancer types, has emerged as a key signaling molecule in carcinogenesis (8,9). Collagen binding to DDR2 activates its tyrosine kinase activity to initiate canonical pathways such as ERK/MAPK and PI3K/AKT signaling cascades (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

The roles of DDR2 and substrate stiffness on cancer cell transcriptome and proliferation

Vessella,

Xiang,

Xiao

et al. 2023

Preprint

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The interactions between cancer cells and the ECM regulate carcinogenesis. The collagen receptor kinase DDR2 is dysregulated in certain cancer cells, but its precise role in these malignancies remains unclear. In this study, we perform RNA-seq to determine how DDR2 and the biomechanical environment regulate cancer cell behaviors. We show that DDR2 knockdown in SH-SY5Y neuroblastoma cells inhibits proliferation and promotes senescence by regulating relevant genes. Increasing substrate stiffness reduces proliferation and promotes cell spreading but does not change senescence or transcriptome. Furthermore, DDR2 knockdown modulates cellular responses to substrate stiffness changes, unraveling a crosstalk between DDR2 and mechanosensing. These findings indicate DDR2 and ECM biomechanics regulate cancer cell behavior through distinct mechanisms, providing new mechanistic insights of cancer progression.

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DDR1 and DDR2: a review on signaling pathway and small molecule inhibitors as an anticancer agent

Cited by 20 publications

References 96 publications

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

The influence of discoidin domain receptor 1 expression on angiogenic factors: VEGF-A and FGF-2 in non-small cell lung cancer

The roles of DDR2 and substrate stiffness on cancer cell transcriptome and proliferation

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