Translational Models in Oncology

Cancer-associated fibroblasts (CAFs) play a crucial role in creating a pro-tumorigenic microenvironment by altering extracellular matrix (ECM) deposition and remodeling (desmoplasia).

This dense stroma can enable cancer cells to evade growth suppressors, promote invasion and metastasis, act as a barrier to drug diffusion, and reduce immune responses. As such, targeting CAFs and CAF-derived ECM presents a promising strategy for optimizing cancer therapies.

However, the heterogeneity of CAFs within and between individual tissues—including their collagen production and contribution to desmoplasia—poses significant challenges to this approach.

The SiaJ model is also an effective platform for testing the efficacy of anti-fibrotic compounds. For example, the small molecule ALK5i, a TGF-β receptor inhibitor, reduces PRO-C3 (nordicPRO-C3™) levels to baseline or even lower after treatment. Additionally, biological compounds such as the anti-TGF-β antibody Fresolimumab demonstrate efficacy in the SiaJ model, by reducing PRO-C1, nordicPRO-C3™ and nordicPRO-C6™ in a dose-dependent manner, dependent on the CAF type.

Nordic Bioscience’s innovative Nordic ProteinFingerPrint™ biomarkers provide critical insights into CAF heterogeneity and fibrotic activity. By leveraging the SiaJ model, we can better understand the tumor microenvironment and evaluate the effectiveness of therapeutic interventions, ultimately helping patients by advancing the fight against cancer.