Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
November-2025 Volume 30 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2025 Volume 30 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review)

  • Authors:
    • Tong Lu
    • Huiying Guo
    • Hang Gong
    • Yaohui Ma
    • Yonggang Tian
    • Dekui Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Emergency Intensive Care Unit, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China
    Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 532
    |
    Published online on: September 18, 2025
       https://doi.org/10.3892/ol.2025.15279
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Cancer is one of the major areas on which global medical research and treatment development are currently focused. There has been an increasing incidence of several types of cancer, such as breast cancer, pancreatic cancer, uterine cancer, prostate cancer, liver cancer, kidney cancer, human papillomavirus‑associated oral cancer and melanoma. Advancements in biomedical research have expanded treatment options for numerous cancers; however, an ideal or definitive cure remains elusive. Therefore, identifying novel targets for cancer treatment has become a major area of research in biomedicine. Due to its involvement in several human diseases and tumor progression, discoidin domain receptor tyrosine kinase 2 (DDR2) has attracted considerable attention. The present review synthesizes findings from previous studies and highlights the recent advances in DDR2 research, assesses its role across different types of tumors and evaluates its emerging significance in multiple biomedical fields.
View Figures

Figure 1

Differential expression of DDR2
between different cancer tumors and normal tissues. Distributions
of gene expression levels are displayed using box plots. The
statistical significance was assessed using the Wilcoxon rank-sum
test. **P<0.01; ***P<0.001. DDR2, discoidin domain receptor
tyrosine kinase 2; TPM, transcripts per million.

Figure 2

Functions of DDR2 in certain solid
tumors. DDR2 promotes the progression of cancer cells through
multiple pathways in several tumors. DDR2, discoidin domain
receptor tyrosine kinase 2; TME, tumor microenvironment; EMT,
epithelial-mesenchymal transition.
View References

1 

Li D, Cao D, Sun Y, Cui Y, Zhang Y, Jiang J and Cao X: The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy. Front Immunol. 15:13316412024. View Article : Google Scholar : PubMed/NCBI

2 

Siegel RL, Giaquinto AN and Jemal A: Cancer statistics, 2024. CA Cancer J Clin. 74:12–49. 2024.PubMed/NCBI

3 

Lane DS and Smith RA: Cancer screening: Patient and population strategies. Med Clin North Am. 107:989–999. 2023. View Article : Google Scholar : PubMed/NCBI

4 

Mamun TI, Younus S and Rahman MH: Gastric cancer-Epidemiology, modifiable and non-modifiable risk factors, challenges and opportunities: An updated review. Cancer Treat Res Commun. 41:1008452024.PubMed/NCBI

5 

Alessa AM and Khan AS: Epidemiology of colorectal cancer in Saudi Arabia: A review. Cureus. 16:e645642024.PubMed/NCBI

6 

Strzelec B, Chmielewski PP and Kielan W: Esophageal cancer: Current status and new insights from inflammatory markers-a brief review. Pol Przegl Chir. 96:83–87. 2024. View Article : Google Scholar : PubMed/NCBI

7 

Liang Z, Zheng X, Li M and Liu M: Improving the prognosis of pancreatic cancer: Insights from epidemiology, genomic alterations, and therapeutic challenges. Front Med. 17:1135–1169. 2023. View Article : Google Scholar : PubMed/NCBI

8 

Webb PM and Jordan SJ: Global epidemiology of epithelial ovarian cancer. Nat Rev Clin Oncol. 21:389–400. 2024. View Article : Google Scholar : PubMed/NCBI

9 

Gu Y, Mu Q and Cheng D: Androgens in cervical cancer: Their role in epidemiology and biology. iScience. 27:1101552024. View Article : Google Scholar : PubMed/NCBI

10 

Cirillo L, Innocenti S and Becherucci F: Global epidemiology of kidney cancer. Nephrol Dial Transplant. 39:920–928. 2024. View Article : Google Scholar : PubMed/NCBI

11 

Thomas A, Douglas E, Reis-Filho JS, Gurcan MN and Wen HY: Metaplastic breast cancer: Current understanding and future directions. Clin Breast Cancer. 23:775–783. 2023. View Article : Google Scholar : PubMed/NCBI

12 

Hasson RM, Bridges CJ, Curley RJ and Erhunmwunsee L: Access to lung cancer screening. Thorac Surg Clin. 33:353–363. 2023. View Article : Google Scholar : PubMed/NCBI

13 

Culp MB, Soerjomataram I, Efstathiou JA, Bray F and Jemal A: Recent global patterns in prostate cancer incidence and mortality rates. Eur Urol. 77:38–52. 2020. View Article : Google Scholar : PubMed/NCBI

14 

Zhang L, Feng Q, Wang J, Tan Z, Li Q and Ge M: Molecular basis and targeted therapy in thyroid cancer: Progress and opportunities. Biochim Biophys Acta Rev Cancer. 1878:1889282023. View Article : Google Scholar : PubMed/NCBI

15 

Connal S, Cameron JM, Sala A, Brennan PM, Palmer DS, Palmer JD, Perlow H and Baker MJ: Liquid biopsies: The future of cancer early detection. J Transl Med. 21:1182023. View Article : Google Scholar : PubMed/NCBI

16 

Zhou Y, Tao L, Qiu J, Xu J, Yang X, Zhang Y, Tian X, Guan X, Cen X and Zhao Y: Tumor biomarkers for diagnosis, prognosis and targeted therapy. Signal Transduct Target Ther. 9:1322024. View Article : Google Scholar : PubMed/NCBI

17 

Waarts MR, Stonestrom AJ, Park YC and Levine RL: Targeting mutations in cancer. J Clin Invest. 132:e1549432022. View Article : Google Scholar : PubMed/NCBI

18 

Passaro A, Al Bakir M, Hamilton EG, Diehn M, André F, Roy-Chowdhuri S, Mountzios G, Wistuba II, Swanton C and Peters S: Cancer biomarkers: Emerging trends and clinical implications for personalized treatment. Cell. 187:1617–1635. 2024. View Article : Google Scholar : PubMed/NCBI

19 

Zaidi SA, Shahzad F and Batool S: Progress in cancer biomarkers monitoring strategies using graphene modified support materials. Talanta. 210:1206692020. View Article : Google Scholar : PubMed/NCBI

20 

Chen L, Kong X, Fang Y, Paunikar S, Wang X, Brown JAL, Bourke E, Li X and Wang J: Recent advances in the role of discoidin domain receptor tyrosine kinase 1 and discoidin domain receptor tyrosine kinase 2 in breast and ovarian cancer. Front Cell Dev Biol. 9:7473142021. View Article : Google Scholar : PubMed/NCBI

21 

Agarwal G, Smith AW and Jones B: Discoidin domain receptors: Micro insights into macro assemblies. Biochim Biophys Acta Mol Cell Res. 1866:1184962019. View Article : Google Scholar : PubMed/NCBI

22 

Elkamhawy A, Lu Q, Nada H, Woo J, Quan G and Lee K: The Journey of DDR1 and DDR2 kinase inhibitors as rising stars in the fight against cancer. Int J Mol Sci. 22:65352021. View Article : Google Scholar : PubMed/NCBI

23 

Mariadoss AVA and Wang CZ: Exploring the cellular and molecular mechanism of discoidin domain receptors (DDR1 and DDR2) in bone formation, regeneration, and its associated disease conditions. Int J Mol Sci. 24:148952023. View Article : Google Scholar : PubMed/NCBI

24 

Zeltz C, Kusche-Gullberg M, Heljasvaara R and Gullberg D: Novel roles for cooperating collagen receptor families in fibrotic niches. Curr Opin Cell Biol. 85:1022732023. View Article : Google Scholar : PubMed/NCBI

25 

Gao Y, Zhou J and Li J: Discoidin domain receptors orchestrate cancer progression: A focus on cancer therapies. Cancer Sci. 112:962–969. 2021. View Article : Google Scholar : PubMed/NCBI

26 

Shimizu T, Kato Y, Sakai Y, Hisamoto N and Matsumoto K: N-Glycosylation of the Discoidin domain receptor is required for axon regeneration in caenorhabditis elegans. Genetics. 213:491–500. 2019. View Article : Google Scholar : PubMed/NCBI

27 

Olaso E, Ikeda K, Eng FJ, Xu L, Wang LH, Lin HC and Friedman SL: DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest. 108:1369–1378. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Juurikka K, Butler GS, Salo T, Nyberg P and Åström P: The role of MMP8 in cancer: A systematic review. Int J Mol Sci. 20:45062019. View Article : Google Scholar : PubMed/NCBI

29 

Gong H, Xu HM and Zhang DK: Focusing on discoidin domain receptors in premalignant and malignant liver diseases. Front Oncol. 13:11236382023. View Article : Google Scholar : PubMed/NCBI

30 

Schab AM, Greenwade MM, Stock E, Lomonosova E, Cho K, Grither WR, Noia H, Wilke D, Mullen MM, Hagemann AR, et al: Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins. Mol Cancer Res. 21:1234–1248. 2023. View Article : Google Scholar : PubMed/NCBI

31 

Wu C, Ying J, Dai M, Peng J and Zhang D: Co-expression of DDR2 and IFITM1 promotes breast cancer cell proliferation, migration and invasion and inhibits apoptosis. J Cancer Res Clin Oncol. 148:3385–3398. 2022. View Article : Google Scholar : PubMed/NCBI

32 

Fathi Z, Mousavi SAJ, Roudi R and Ghazi F: Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients. PLoS One. 13:e02006332018. View Article : Google Scholar : PubMed/NCBI

33 

Sun M and Shen Z: Knockdown of long non-coding RNA (lncRNA) Colon cancer-associated transcript-1 (CCAT1) suppresses oral squamous cell carcinoma proliferation, invasion, and migration by inhibiting the discoidin domain receptor 2 (DDR2)/ERK/AKT Axis. Med Sci Monit. 26:e9200202020.PubMed/NCBI

34 

Sideris M, Menon U and Manchanda R: Screening and prevention of ovarian cancer. Med J Aust. 220:264–274. 2024. View Article : Google Scholar : PubMed/NCBI

35 

Veneziani AC, Gonzalez-Ochoa E, Alqaisi H, Madariaga A, Bhat G, Rouzbahman M, Sneha S and Oza AM: Heterogeneity and treatment landscape of ovarian carcinoma. Nat Rev Clin Oncol. 20:820–842. 2023. View Article : Google Scholar : PubMed/NCBI

36 

Schab AM, Greenwade MM, Stock E, Lomonosova E, Cho K, Grither WR, Noia H, Wilke D, Mullen MM, Hagemann AR, et al: Stromal DDR2 promotes ovarian cancer metastasis through regulation of metabolism and secretion of extracellular matrix proteins. Mol Cancer Res. 21:1234–1248. 2023. View Article : Google Scholar : PubMed/NCBI

37 

Yuan WC, Zhang JX, Chen HB, Yuan Y, Zhuang YP, Zhou HL, Li MH, Qiu WL and Zhou HG: A bibliometric and visual analysis of cancer-associated fibroblasts. Front Immunol. 14:13231152023. View Article : Google Scholar : PubMed/NCBI

38 

Akinjiyan FA, Ibitoye Z, Zhao P, Shriver LP, Patti GJ, Longmore GD and Fuh KC: DDR2-regulated arginase activity in ovarian cancer-associated fibroblasts promotes collagen production and tumor progression. Oncogene. 43:189–201. 2024. View Article : Google Scholar : PubMed/NCBI

39 

Arumi-Planas M, Rodriguez-Baena FJ, Cabello-Torres F, Gracia F, Lopez-Blau C, Nieto MA and Sanchez-Laorden B: Microenvironmental Snail1-induced immunosuppression promotes melanoma growth. Oncogene. 42:2659–2672. 2023. View Article : Google Scholar : PubMed/NCBI

40 

Baulida J and García de Herreros A: Snail1-driven plasticity of epithelial and mesenchymal cells sustains cancer malignancy. Biochim Biophys Acta. 1856:55–61. 2015.PubMed/NCBI

41 

Dasari S and Tchounwou PB: Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 740:364–378. 2014. View Article : Google Scholar : PubMed/NCBI

42 

Li F, Zheng Z, Chen W, Li D, Zhang H, Zhu Y, Mo Q, Zhao X, Fan Q, Deng F, et al: Regulation of cisplatin resistance in bladder cancer by epigenetic mechanisms. Drug Resist Updat. 68:1009382023. View Article : Google Scholar : PubMed/NCBI

43 

Heiserman JP, Nallanthighal S, Gifford CC, Graham K, Samarakoon R, Gao C, Sage JJ, Zhang W, Higgins PJ and Cheon DJ: Heat shock protein 27, a novel downstream target of collagen type XI alpha 1, synergizes with fatty acid oxidation to confer cisplatin resistance in ovarian cancer cells. Cancers (Basel). 13:48552021. View Article : Google Scholar : PubMed/NCBI

44 

Yang L, Hu Q and Huang T: Breast cancer treatment strategies targeting the tumor microenvironment: How to Convert ‘Cold’ Tumors to ‘Hot’ Tumors. Int J Mol Sci. 25:72082024. View Article : Google Scholar : PubMed/NCBI

45 

Corsa CA, Brenot A, Grither WR, Van Hove S, Loza AJ, Zhang K, Ponik SM, Liu Y, DeNardo DG, Eliceiri KW, et al: The action of discoidin domain receptor 2 in basal tumor cells and stromal Cancer-associated fibroblasts is critical for breast cancer metastasis. Cell Rep. 15:2510–2523. 2016. View Article : Google Scholar : PubMed/NCBI

46 

Lin CC, Yang WH, Lin YT, Tang X, Chen PH, Ding CC, Qu DC, Alvarez JV and Chi JT: DDR2 upregulation confers ferroptosis susceptibility of recurrent breast tumors through the Hippo pathway. Oncogene. 40:2018–2034. 2021. View Article : Google Scholar : PubMed/NCBI

47 

Zhou Q, Meng Y, Li D, Yao L, Le J, Liu Y, Sun Y, Zeng F, Chen X and Deng G: Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies. Signal Transduct Target Ther. 9:552024. View Article : Google Scholar : PubMed/NCBI

48 

Carvalho FM: Triple-negative breast cancer: From none to multiple therapeutic targets in two decades. Front Oncol. 13:12447812023. View Article : Google Scholar : PubMed/NCBI

49 

Varzaru VB, Vlad T, Popescu R, Vlad CS, Moatar AE and Cobec IM: Triple-negative breast cancer: Molecular particularities still a challenge. Diagnostics (Basel). 14:18752024. View Article : Google Scholar : PubMed/NCBI

50 

Toy KA, Valiathan RR, Núñez F, Kidwell KM, Gonzalez ME, Fridman R and Kleer CG: Tyrosine kinase discoidin domain receptors DDR1 and DDR2 are coordinately deregulated in triple-negative breast cancer. Breast Cancer Res Treat. 150:9–18. 2015. View Article : Google Scholar : PubMed/NCBI

51 

Rao X, Zhang C, Luo H, Zhang J, Zhuang Z, Liang Z and Wu X: Targeting gastric cancer stem cells to enhance treatment response. Cells. 11:28282022. View Article : Google Scholar : PubMed/NCBI

52 

Li Z, Wang J, Wang Z and Xu Y: Towards an optimal model for gastric cancer peritoneal metastasis: Current challenges and future directions. EBioMedicine. 92:1046012023. View Article : Google Scholar : PubMed/NCBI

53 

Yao X, Ajani JA and Song S: Molecular biology and immunology of gastric cancer peritoneal metastasis. Transl Gastroenterol Hepatol. 5:572020. View Article : Google Scholar : PubMed/NCBI

54 

Kurashige J, Hasegawa T, Niida A, Sugimachi K, Deng N, Mima K, Uchi R, Sawada G, Takahashi Y, Eguchi H, et al: Integrated molecular profiling of human gastric cancer identifies DDR2 as a potential regulator of peritoneal dissemination. Sci Rep. 6:223712016. View Article : Google Scholar : PubMed/NCBI

55 

Wang YG, Xu L, Jia RR, Wu Q, Wang T, Wei J, Ma JL, Shi M and Li ZS: DDR2 induces gastric cancer cell activities via activating mTORC2 signaling and is associated with clinicopathological characteristics of gastric cancer. Dig Dis Sci. 61:2272–2283. 2016. View Article : Google Scholar : PubMed/NCBI

56 

Firouzjaei AA, Aghaee-Bakhtiari SH, Tafti A, Sharifi K, Abadi MHJN, Rezaei S and Mohammadi-Yeganeh S: Impact of curcumin on ferroptosis-related genes in colorectal cancer: Insights from in-silico and in-vitro studies. Cell Biochem Funct. 41:1488–1502. 2023. View Article : Google Scholar : PubMed/NCBI

57 

Ruff SM, Brown ZJ and Pawlik TM: A review of targeted therapy and immune checkpoint inhibitors for metastatic colorectal cancer. Surg Oncol. 51:1019932023. View Article : Google Scholar : PubMed/NCBI

58 

Lafitte M, Sirvent A and Roche S: Collagen kinase receptors as potential therapeutic targets in metastatic colon cancer. Front Oncol. 10:1252020. View Article : Google Scholar : PubMed/NCBI

59 

Beauchemin N: The colorectal tumor microenvironment: The next decade. Cancer Microenviron. 4:181–185. 2011. View Article : Google Scholar : PubMed/NCBI

60 

Xu X, Duan X, Wang S, Zhang Y, Gao Y, Xu X, Yeerkenbieke G, Zhou J and Li J: Special issue ‘The advance of solid tumor research in China’: Discoidin domain receptor 2 promotes colorectal cancer metastasis by regulating epithelial mesenchymal transition via activating AKT signaling. Int J Cancer. 152:51–65. 2023. View Article : Google Scholar : PubMed/NCBI

61 

Chidambaranathan-Reghupaty S, Fisher PB and Sarkar D: Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv Cancer Res. 149:1–61. 2021. View Article : Google Scholar : PubMed/NCBI

62 

Piñero F, Dirchwolf M and Pessôa MG: Biomarkers in hepatocellular carcinoma: Diagnosis, prognosis and treatment response assessment. Cells. 9:13702020. View Article : Google Scholar : PubMed/NCBI

63 

Wu L, Zhao X, Ma H, Zhang L and Li X: Discoidin domain receptor 1, a potential biomarker and therapeutic target in hepatocellular carcinoma. Int J Gen Med. 15:2037–2044. 2022. View Article : Google Scholar : PubMed/NCBI

64 

Park JW, Lee YS, Kim JS, Lee SK, Kim BH, Lee JA, Lee NO, Kim SH and Hong EK: Downregulation of discoidin domain receptor 2 decreases tumor growth of hepatocellular carcinoma. J Cancer Res Clin Oncol. 141:1973–1983. 2015. View Article : Google Scholar : PubMed/NCBI

65 

Xie B, Lin W, Ye J, Wang X, Zhang B, Xiong S, Li H and Tan G: DDR2 facilitates hepatocellular carcinoma invasion and metastasis via activating ERK signaling and stabilizing SNAIL1. J Exp Clin Cancer Res. 34:1012015. View Article : Google Scholar : PubMed/NCBI

66 

Tang Q, Chen Y, Li X, Long S, Shi Y, Yu Y, Wu W, Han L and Wang S: The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers. Front Immunol. 13:9644422022. View Article : Google Scholar : PubMed/NCBI

67 

Hao L, Li S and Deng J: The current status and future of PD-L1 in liver cancer. Front Immunol. 14:13235812023. View Article : Google Scholar : PubMed/NCBI

68 

Wen Q, Han T, Wang Z and Jiang S: Role and mechanism of programmed death-ligand 1 in hypoxia-induced liver cancer immune escape. Oncol Lett. 19:2595–2601. 2020.PubMed/NCBI

69 

Kang L, Tian Y, Xu S and Chen H: Oxaliplatin-induced peripheral neuropathy: Clinical features, mechanisms, prevention and treatment. J Neurol. 268:3269–3282. 2021. View Article : Google Scholar : PubMed/NCBI

70 

Liu W, Zhang F, Quan B, Yao F, Chen R, Ren Z, Dong L and Yin X: DDR2/STAT3 positive feedback loop mediates the immunosuppressive microenvironment by upregulating PD-L1 and recruiting MDSCs in Oxaliplatin-resistant HCC. Cell Mol Gastroenterol Hepatol. 18:1013772024. View Article : Google Scholar : PubMed/NCBI

71 

Li K, Shi H, Zhang B, Ou X, Ma Q, Chen Y, Shu P, Li D and Wang Y: Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer. Signal Transduct Target Ther. 6:3622021. View Article : Google Scholar : PubMed/NCBI

72 

Li Q, Chen K, Zhang T, Jiang D, Chen L, Jiang J, Zhang C and Li S: Understanding sorafenib-induced ferroptosis and resistance mechanisms: Implications for cancer therapy. Eur J Pharmacol. 955:1759132023. View Article : Google Scholar : PubMed/NCBI

73 

Tang W, Chen Z, Zhang W, Cheng Y, Zhang B, Wu F, Wang Q, Wang S, Rong D, Reiter FP, et al: The mechanisms of sorafenib resistance in hepatocellular carcinoma: Theoretical basis and therapeutic aspects. Signal Transduct Target Ther. 5:872020. View Article : Google Scholar : PubMed/NCBI

74 

Liu QQ, Liu YW, Xie YK, Zhang JH, Song CX, Wang JZ and Xie BH: Amplification of DDR2 mediates sorafenib resistance through NF-κB/c-Rel signaling in hepatocellular carcinoma. Cell Biol Int. 45:1906–1916. 2021. View Article : Google Scholar : PubMed/NCBI

75 

Cai Y, Lyu T, Li H, Liu C, Xie K, Xu L, Li W, Liu H, Zhu J, Lyu Y, et al: LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC. J Exp Clin Cancer Res. 41:3352022. View Article : Google Scholar : PubMed/NCBI

76 

Chung C, Boterberg T, Lucas J, Panoff J, Valteau-Couanet D, Hero B, Bagatell R and Hill-Kayser CE: Neuroblastoma. Pediatr Blood Cancer. 68 (Suppl 2):e284732021. View Article : Google Scholar : PubMed/NCBI

77 

Vessella T, Xiang S, Xiao C, Stilwell M, Fok J, Shohet J, Rozen E, Zhou HS and Wen Q: DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms. FEBS Open Bio. 14:867–882. 2024. View Article : Google Scholar : PubMed/NCBI

78 

Karam JA, Msaouel P, Haymaker CL, Matin SF, Campbell MT, Zurita AJ, Shah AY, Wistuba II, Marmonti E, Duose DY, et al: Phase II trial of neoadjuvant sitravatinib plus nivolumab in patients undergoing nephrectomy for locally advanced clear cell renal cell carcinoma. Nat Commun. 14:26842023. View Article : Google Scholar : PubMed/NCBI

79 

Rozen EJ, Frantz W, Wigglesworth K, Vessella T, Zhou HS and Shohet JM: Blockade of discoidin domain receptor signaling with sitravatinib reveals DDR2 as a mediator of neuroblastoma pathogenesis and metastasis. Mol Cancer Ther. 23:1124–1138. 2024. View Article : Google Scholar : PubMed/NCBI

80 

Agosto Salgado S, Kaye ER, Sargi Z, Chung CH and Papaleontiou M: Management of advanced thyroid cancer: Overview, advances, and opportunities. Am Soc Clin Oncol Educ Book. 43:e3897082023. View Article : Google Scholar : PubMed/NCBI

81 

Lam AK: Papillary thyroid carcinoma: Current position in epidemiology, genomics, and classification. Methods Mol Biol. 2534:1–15. 2022. View Article : Google Scholar : PubMed/NCBI

82 

Liang Z, Xie WJ, Zhao M, Cheng GP and Wu MJ: DDR2 facilitates papillary thyroid carcinoma epithelial mesenchymal transition by activating ERK2/Snail1 pathway. Oncol Lett. 14:8114–8121. 2017.PubMed/NCBI

83 

Wilson TK and Zishiri OT: Prostate cancer: A review of genetics, current biomarkers and personalised treatments. Cancer Rep (Hoboken). 7:e700162024.PubMed/NCBI

84 

Nevo A, Navaratnam A and Andrews P: Prostate cancer and the role of biomarkers. Abdom Radiol (NY). 45:2120–2132. 2020. View Article : Google Scholar : PubMed/NCBI

85 

Azemikhah M, Ashtiani HA, Aghaei M and Rastegar H: Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues. Res Pharm Sci. 10:356–363. 2015.PubMed/NCBI

86 

Huang RH, Ge ZL, Xu G, Zeng QM, Jiang B, Xiao GC, Xia W, Wu YT and Liao YF: Prognosis and diagnosis of prostate cancer based on hypergraph regularization sparse least partial squares regression algorithm. Aging (Albany NY). 16:9599–9624. 2024. View Article : Google Scholar : PubMed/NCBI

87 

Yan Z, Jin S, Wei Z, Huilian H, Zhanhai Y, Yue T, Juan L, Jing L, Libo Y and Xu L: Discoidin domain receptor 2 facilitates prostate cancer bone metastasis via regulating parathyroid hormone-related protein. Biochim Biophys Acta. 1842:1350–1363. 2014. View Article : Google Scholar : PubMed/NCBI

88 

Tang G, Liu J, Qi L and Li Y: The evolving role of checkpoint inhibitors in the treatment of urothelial carcinoma. Br J Clin Pharmacol. 89:93–113. 2023. View Article : Google Scholar : PubMed/NCBI

89 

Tsai MC, Li WM, Huang CN, Ke HL, Li CC, Yeh HC, Chan TC, Liang PI, Yeh BW, Wu WJ, et al: DDR2 overexpression in urothelial carcinoma indicates an unfavorable prognosis: A large cohort study. Oncotarget. 7:78918–78931. 2016. View Article : Google Scholar : PubMed/NCBI

90 

Cario M: DDR1 and DDR2 in skin. Cell Adh Migr. 12:386–393. 2018.PubMed/NCBI

91 

Sala M, Allain N, Moreau M, Jabouille A, Henriet E, Abou-Hammoud A, Uguen A, Di-Tommaso S, Dourthe C, Raymond AA, et al: Discoidin domain receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation. Oncogene. 41:2571–2586. 2022. View Article : Google Scholar : PubMed/NCBI

92 

Poudel B, Lee YM and Kim DK: DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway. Acta Biochim Biophys Sin (Shanghai). 47:292–298. 2015. View Article : Google Scholar : PubMed/NCBI

93 

Xiao Y and Yu D: Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 221:1077532021. View Article : Google Scholar : PubMed/NCBI

94 

Fu X, He Y, Li M, Huang Z and Najafi M: Targeting of the tumor microenvironment by curcumin. Biofactors. 47:914–932. 2021. View Article : Google Scholar : PubMed/NCBI

95 

Huang J, Zhang L, Wan D, Zhou L, Zheng S, Lin S and Qiao Y: Extracellular matrix and its therapeutic potential for cancer treatment. Signal Transduct Target Ther. 6:1532021. View Article : Google Scholar : PubMed/NCBI

96 

Jiang Y, Zhang H, Wang J, Liu Y, Luo T and Hua H: Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy. J Hematol Oncol. 15:342022. View Article : Google Scholar : PubMed/NCBI

97 

Yuan Z, Li Y, Zhang S, Wang X, Dou H, Yu X, Zhang Z, Yang S and Xiao M: Extracellular matrix remodeling in tumor progression and immune escape: From mechanisms to treatments. Mol Cancer. 22:482023. View Article : Google Scholar : PubMed/NCBI

98 

Prakash J and Shaked Y: The Interplay between extracellular matrix remodeling and cancer therapeutics. Cancer Discov. 14:1375–1388. 2024. View Article : Google Scholar : PubMed/NCBI

99 

Borza CM and Pozzi A: Discoidin domain receptors in disease. Matrix Biol. 34:185–192. 2014. View Article : Google Scholar : PubMed/NCBI

100 

Chen Y, McAndrews KM and Kalluri R: Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Rev Clin Oncol. 18:792–804. 2021. View Article : Google Scholar : PubMed/NCBI

101 

Zhang H, Yue X, Chen Z, Liu C, Wu W, Zhang N, Liu Z, Yang L, Jiang Q, Cheng Q, et al: Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: New opportunities in cancer immunotherapy and advances in clinical trials. Mol Cancer. 22:1592023. View Article : Google Scholar : PubMed/NCBI

102 

Wright K, Ly T, Kriet M, Czirok A and Thomas SM: Cancer-associated fibroblasts: Master tumor microenvironment modifiers. Cancers (Basel). 15:18992023. View Article : Google Scholar : PubMed/NCBI

103 

Yamamoto Y, Kasashima H, Fukui Y, Tsujio G, Yashiro M and Maeda K: The heterogeneity of cancer-associated fibroblast subpopulations: Their origins, biomarkers, and roles in the tumor microenvironment. Cancer Sci. 114:16–24. 2023. View Article : Google Scholar : PubMed/NCBI

104 

Akinjiyan FA, Dave RM, Alpert E, Longmore GD and Fuh KC: DDR2 expression in Cancer-associated fibroblasts promotes ovarian cancer tumor invasion and metastasis through periostin-ITGB1. Cancers (Basel). 14:34822022. View Article : Google Scholar : PubMed/NCBI

105 

Barcus CE, Hwang PY, Morikis V, Brenot A, Pence P, Clarke M and Longmore GD: Tyrosine kinase-independent actions of DDR2 in tumor cells and cancer-associated fibroblasts influence tumor invasion, migration and metastasis. J Cell Sci. 134:jcs2584312021. View Article : Google Scholar : PubMed/NCBI

106 

Tang T, Huang X, Zhang G, Hong Z, Bai X and Liang T: Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduct Target Ther. 6:722021. View Article : Google Scholar : PubMed/NCBI

107 

Sun Q, Hong Z, Zhang C, Wang L, Han Z and Ma D: Immune checkpoint therapy for solid tumours: Clinical dilemmas and future trends. Signal Transduct Target Ther. 8:3202023. View Article : Google Scholar : PubMed/NCBI

108 

Labrie M, Brugge JS, Mills GB and Zervantonakis IK: Therapy resistance: Opportunities created by adaptive responses to targeted therapies in cancer. Nat Rev Cancer. 22:323–339. 2022. View Article : Google Scholar : PubMed/NCBI

109 

Rammal H, Saby C, Magnien K, Van-Gulick L, Garnotel R, Buache E, El Btaouri H, Jeannesson P and Morjani H: Discoidin domain receptors: Potential actors and targets in cancer. Front Pharmacol. 7:552016. View Article : Google Scholar : PubMed/NCBI

110 

Reger de Moura C, Prunotto M, Sohail A, Battistella M, Jouenne F, Marbach D, Lebbé C, Fridman R and Mourah S: Discoidin domain receptors in melanoma: Potential therapeutic targets to overcome MAPK inhibitor resistance. Front Oncol. 10:17482020. View Article : Google Scholar : PubMed/NCBI

111 

Lv B, Wang Y, Ma D, Cheng W, Liu J, Yong T, Chen H and Wang C: Immunotherapy: Reshape the tumor immune microenvironment. Front Immunol. 13:8441422022. View Article : Google Scholar : PubMed/NCBI

112 

Fontana R, Mestre-Farrera A and Yang J: Update on Epithelial-Mesenchymal plasticity in cancer progression. Annu Rev Pathol. 19:133–156. 2024. View Article : Google Scholar : PubMed/NCBI

113 

Pharnexcloud Cloud database: CIDD-0108633. https://data.pharnexcloud.com/1/detail/44/b112ca4087d668785e947a57493d1740?detailTitle=CIDD-0108633November 10–2024

114 

Pharnexcloud Cloud database ICP-033. https://data.pharnexcloud.com/1/detail/44/06d801cb636235b298c40029ad9921e7?detailTitle=ICP-033November 10–2024

115 

Pharnexcloud Cloud database BK-40143. https://data.pharnexcloud.com/1/detail/44/654784daf0b133e42d02214b22cb03a6?detailTitle=BK-40143November 10–2024

116 

Pharnexcloud Cloud database PB-1. https://data.pharnexcloud.com/1/detail/44/6368349d3319f374ddfd35dfd477ea29?detailTitle=PB-1November 10–2024

117 

Pharnexcloud Cloud database Dual-DDR1/2inhibitors. https://data.pharnexcloud.com/1/detail/44/06c9c2f149b73e46fba1487930c5acb8?detailTitle=dual%20DDR-1%2F2%20inhibitors%20%28acute%20lung%20injury%2Finflammation%29November 10–2024

118 

Dasatinib. https://data.pharnexcloud.com/1/detail/44/0245952ecff55018e2a459517fdb40e3?detailTitle=dasatinibhttps://data.pharnexcloud.com/1/detail/44/0245952ecff55018e2a459517fdb40e3?detailTitle=dasatinibNovember 10–2024

119 

Trono P, Ottavi F and Rosano' L: Novel insights into the role of Discoidin domain receptor 2 (DDR2) in cancer progression: A new avenue of therapeutic intervention. Matrix Biol. 125:31–39. 2024. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lu T, Guo H, Gong H, Ma Y, Tian Y and Zhang D: Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review). Oncol Lett 30: 532, 2025.
APA
Lu, T., Guo, H., Gong, H., Ma, Y., Tian, Y., & Zhang, D. (2025). Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review). Oncology Letters, 30, 532. https://doi.org/10.3892/ol.2025.15279
MLA
Lu, T., Guo, H., Gong, H., Ma, Y., Tian, Y., Zhang, D."Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review)". Oncology Letters 30.5 (2025): 532.
Chicago
Lu, T., Guo, H., Gong, H., Ma, Y., Tian, Y., Zhang, D."Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review)". Oncology Letters 30, no. 5 (2025): 532. https://doi.org/10.3892/ol.2025.15279
Copy and paste a formatted citation
x
Spandidos Publications style
Lu T, Guo H, Gong H, Ma Y, Tian Y and Zhang D: Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review). Oncol Lett 30: 532, 2025.
APA
Lu, T., Guo, H., Gong, H., Ma, Y., Tian, Y., & Zhang, D. (2025). Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review). Oncology Letters, 30, 532. https://doi.org/10.3892/ol.2025.15279
MLA
Lu, T., Guo, H., Gong, H., Ma, Y., Tian, Y., Zhang, D."Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review)". Oncology Letters 30.5 (2025): 532.
Chicago
Lu, T., Guo, H., Gong, H., Ma, Y., Tian, Y., Zhang, D."Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review)". Oncology Letters 30, no. 5 (2025): 532. https://doi.org/10.3892/ol.2025.15279
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team