Exploration of Targeted Anti-tumor Therapy

Table 1. PGs and GAGs as biomarkers across cancer contexts.

Molecule	Cancer context	Biomarker type	Key observation	Interpretation	References
GPC3	HCC	Diagnostic/circulating	Variable serum-tissue correlation	Compartment-dependent detectability and tumor heterogeneity	[22, 29, 30]
SDC1	Multiple cancers, CRC	Circulating/prognostic	Elevated plasma levels linked to survival	Composite marker of tumor activity, ECM remodeling, and glycocalyx damage	[18–20]
SDC4	Breast cancer	Risk/early biomarker potential	Higher pre-diagnostic serum levels associated with subsequent breast cancer risk	Potential circulating biomarker requiring further validation	[18]
VCAN	Stromal-rich tumors	Stromal/prognostic	Accumulates in CAF-rich regions	Marker of desmoplasia and immune-modulating ECM	[11, 31]
CSPG4 (NG2)	Melanoma, HCC, TNBC	Surface/EV biomarker	Detected on tumor cells and EVs	Reflects invasive phenotype and tumor-ECM interactions	[39]
DCN	Multiple cancers	Stromal/prognostic	Reduced in aggressive tumors	Loss of tumor-suppressive ECM regulation	[10, 26]
BGN	Osteosarcoma, gastric cancer	Circulating/functional	Elevated and signaling-active	Reflects ECM remodeling and pathway activation	[27, 33]
Perlecan (HSPG2)	Angiogenic tumors	Matrix-associated	Intact vs. fragment dual roles	Distinguishes pro- vs. anti-angiogenic states	[34, 35]
PG-derived heparan sulfate fragments	Multiple cancers	Circulating/inflammatory	Released during ECM remodeling	Indicator of glycan turnover and inflammation	[36, 37]

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GAGs: glycosaminoglycans; GPC3: glypican-3: SDC1: syndecan-1; CRC: colorectal carcinoma; ECM: extracellular matrix; VCAN: versican; CAF: cancer-associated fibroblast; CSPG4: chondroitin sulfate proteoglycan 4; HCC: hepatocellular carcinoma; TNBC: triple-negative breast cancer; DCN: decorin; BGN: biglycan; HSPG2: heparan sulfate proteoglycan 2.

Declarations

Acknowledgements

During the preparation of this work, the authors used ChatGPT (OpenAI) to assist with language editing, figure generation, text refinement, and improvement of readability. All scientific concepts, literature selection, interpretation of published findings, critical evaluation of the literature, and conclusions were developed and verified by the authors. Following the use of the tool, the authors reviewed and edited the content as necessary and take full responsibility for the accuracy, originality, and integrity of the published work.

Author contributions

AB: Conceptualization, Investigation, Formal analysis, Visualization, Writing—original draft, Writing—review & editing. IS: Writing—review & editing. AT: Writing—review & editing, Supervision. GT: Conceptualization, Writing—review & editing, Supervision. DN: Conceptualization, Supervision, Writing—review & editing, Project administration, Funding acquisition. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

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Not applicable.

Availability of data and materials

Not applicable.

Funding

This research was partly funded by the Special Account for Research Funds of the University of Crete (SARF UoC) KA 10082 to D.N. The funders had no role in decision to publish, or preparation of the manuscript.

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