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Extracellular matrix and its therapeutic potential for cancer treatment
Open accessAbstract
The extracellular matrix (ECM) is one of the major components of tumors that plays multiple crucial roles, including mechanical support, modulation of the microenvironment, and a source of signaling molecules. The quantity and cross-linking status of ECM components are major factors determining tissue stiffness. During tumorigenesis, the interplay between cancer cells and the tumor microenvironment (TME) often results in the stiffness of the ECM, leading to aberrant mechanotransduction and further malignant transformation. Therefore, a comprehensive understanding of ECM dysregulation in the TME would contribute to the discovery of promising therapeutic targets for cancer treatment. Herein, we summarized the knowledge concerning the following: (1) major ECM constituents and their functions in both normal and malignant conditions; (2) the interplay between cancer cells and the ECM in the TME; (3) key receptors for mechanotransduction and their alteration during carcinogenesis; and (4) the current therapeutic strategies targeting aberrant ECM for cancer treatment.
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“several other ECM components, such as fibronectin, hyaluronan, TGF-β, integrins involved in mechanotransduction, and other sensors of matrix stiffness, are being studied as potential therapeutic targets in various cancers, including CRC [218].”
From Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer (2025) · cites this paper as [218]
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“Several therapeutic approaches have been developed that aim to alleviate excessive collagen deposition in the TME of solid tumors by altering the synthesis, degradation, or crosslinking of collagen [218].”
From Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer (2025) · cites this paper as [218]
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“The ECM's functional characteristics and structural components, such as collagen and proteoglycans, play a critical role in maintaining tissue homeostasis and promoting angiogenesis.”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [5]
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“A key limitation of nanoparticle therapy is heterogeneous tumor deposition driven by weak recognition/internalization and limited traversal through dense ECM [78].”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [78]
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Immune Checkpoint Inhibitors in Cancer Therapy
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“Similarly, EDB can also be used as a target for antibody-mediated radioisotope delivery, and fusion protein I labeling of L19 and small immune protein can not only slow tumor growth but also prolong the survival of F9 teratoma and head and neck cancer xenograft mice [8].”
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Metadata
- Authors
- Huang, J., Zhang, L., Wan, D., Zhou, L., Zheng, S., Lin, S., & Qiao, Y.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Zhejiang Shuren University (CN)
- Corresponding author
- Lin, Shengzhang
- Qiao, Yiting
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2021-04-23
- Volume
- 6
- Issue
- 1
- Pages
- 153-153
- ISSN
- 2059-3635 (ISSN-L)
- PMC
- PMC8062524
- OpenAlex
- W3152880902
- Cited by
- 962
- References
- 588
- Citations by year
- 2026: 206 · 2025: 308 · 2024: 212 · 2023: 136 · 2022: 84 · 2021: 15
- FWCI
- 14.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (2016C04003, 81903143, no.81721091, 81721091, 2017ZX10203205, 91542205)
- Chinese Academy of Medical Sciences ((2019‐I2M‐5‐030))
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- extracellular matrix, tumor microenvironment, tissue stiffness, mechanotransduction, cancer cells, carcinogenesis
- MeSH terms
- Extracellular Matrix, Humans, Neoplasms, Tumor Microenvironment, Carcinogenesis
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