Collagen (COL) (COL)

Collagen is the primary structural component of the extracellular matrix (ECM) and is frequently overexpressed and reorganized in the tumor microenvironment, a phenomenon known as desmoplasia (Baldari et al., 2022, Encyclopedia MDPI). In many solid tumors, such as pancreatic and breast cancer, dense and highly cross-linked collagen fibers create a physical barrier that increases interstitial fluid pressure, thereby hindering the delivery of oxygen, nutrients, and therapeutic agents (Chauhan et al., 2013, PMID: 24084631). Furthermore, collagen acts as a biochemical signal through interactions with receptors like integrins and discoidin domain receptors (DDRs), promoting tumor cell proliferation, survival, and metastasis (Philp et al., 2018, PMID: 29954964). Therapeutic approaches targeting collagen aim to normalize the tumor stroma by either degrading existing collagen fibers using enzymes like collagenase or by inhibiting the synthesis and cross-linking of new collagen via TGF-beta or lysyl oxidase (LOX) inhibitors (Vachhani et al., 2024, PMID: 40241543). While promising for improving drug penetration, these strategies must be carefully managed to avoid systemic toxicity and the potential for facilitating tumor cell escape (Liang et al., 2016, PMID: 27141043).

Other names

Tumor collagenFibrillar collagenExtracellular matrix collagenType I collagenType IV collagenDesmoplastic stroma

Enzymatic degradation of collagen fibers to reduce interstitial fluid pressure and improve drug penetration; inhibition of collagen biosynthesis and cross-linking to normalize the tumor microenvironment and reduce matrix stiffness.