Recent evidence has also shown that CAFs produce minor collagens such as type X, XI, XII and XIV, XVIII, XXI and XXII. The upregulation of these minor collagens (The Minor Collagen Hypothesis) is thought to have profound pathological effects on tumor progression, as these collagens are present only at very low levels in healthy adult humans.

Unfortunately, tumor fibrosis leads to decreased treatment efficacy, as standard-of-care cancer therapies cannot reach tumor cells due to the stromal barrier. Immunotherapies have also been shown to be inhibited by tumor fibrosis, as immune cells (T-cells and NK-cells) become fixed and inactivated in the fibrous tumor microenvironment.

Evidence has shown that clearance of CAFs might not necessarily lead to effective anticancer therapy, but instead requires a shift in certain CAF subtypes. Currently, there is an urgent need for CAF biomarkers that can be used to identify specific CAF subtypes and to identify patients with specific CAF subtypes. Several CAF subtypes have been found to exhibit different collagen expressions. MyCAFs express high levels of COL8A1, COL10A1, COL11A1, and COL12A1, iCAFs express high levels of COL14A1, and stellate-like CAFs express high levels of COL4A1/2 and COL18A1 (Figure 1). In addition to myCAFs, iCAFs, and stellate-like CAFs, other subpopulations also show different collagen expression patterns associated with immunosuppression and response to therapy.

Collagens essential for embryogenesis reoccur in CAF subtypes:
Circulating collagen biomarkers may guide drug development of CAF-modulating therapies (as presented at AACR 2023)

Circulating collagen biomarkers may guide drug development of CAF-modulating therapies

Figure 1.

Nordic Bioscience's CAF biomarkers have high translational value as the same biomarkers can be measured in vitro (supernatant) and in vivo samples (serum/plasma) as well as in human material (serum). Our laboratory services offer customized solutions for your cancer biomarker needs. 

Please don't hesitate to contact us if you have any questions or other inquiries.

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