Cancer is a fibrotic disease. The fibrotic response in the tumor microenvironment is termed desmoplasia and is characterized by excessive turnover and remodeling of the extracellular matrix (ECM). In fibrous tumors, the increased collagen production and crosslinking, as well as altered degradation of the collagenous matrix result in loss of tissue organization and cellular behavior, the release of growth factors, and the generation of cryptic sites on collagens with potent signaling activity. All these collagen alterations drive disease progression, and immune suppression and affect treatment response. Moreover, these extracellular matrix turnover products can be picked up as biomarkers of a specific fibrotic/desmoplastic signature relevant in the clinical setting of oncology.
Albeit tumor fibrosis and cancer-associated fibroblasts clearly impact prognosis and efficacy of intervention, the understanding of tumor fibrosis and cancer-associated fibroblasts is only in its infancy. There is a desperate need for tools that can be applied in the clinical setting to bridge classical tumor biology and desmoplasia. Such biomarkers have the potential to greatly benefit patients, by aiding in patient stratification and directing the most appropriate treatment, or combination of treatments, at the right time, to the right patients. Use of such predictive or prognostic biomarkers to enrich or stratify patients likely to respond to a therapeutic in drug development trials, may not only reduce trial length and size required to determine therapeutic efficacy but will also spare patients for treatment with a poor chance of being effective.
Specific collagen fragments released to the circulation as a consequence of the tumor tissue remodeling and desmoplastic reaction are measurable in serum with the Nordic ProteinFingerPrint Technology™. Our lab services include quantification of the desmoplastic reaction and stromal reactivity (collagen turnover) it may be possible to phenotype patients and select those most likely to respond to a given treatment.
Serum fibrosis biomarkers predict prognosis and therapy resistance in cancer patients
Cancer-associated fibroblasts (CAFs) are a potential target for optimizing therapeutic strategies against cancer and attempts to modulate CAFs for therapeutic benefit are ongoing. Nonetheless, limitations in our current understanding of CAFs challenge this strategy. Moreover, the growing focus on immune suppression and therapy resistance has led to increased (re)-focus on transforming growth factor beta (TGF-β) for understanding cancer phenotypes. TGF-β is associated with immune exclusion, is secreted by cancer-associated fibroblasts and other stromal cells, and is considered the major inducer of fibrogenesis.
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The Scar-in-a-Jar translational model and associated Nordic ProteinFingerPrint Technology™ biomarkers offer a simple translational in vitro tool to address CAF biology and the direct impact of therapeutic intervention, in particular related to extracellular matrix remodeling.
Nordic ProteinFingerPrint Technology™ biomarkers measured in serum are associated with disease activity. Evidence supports that changes in these biomarkers towards normalization are indicative of response and/or maintenance of no evidence of disease whereas increases in such biomarkers may be indicative of progression even prior to clinical manifestation. Understanding how therapies may potentially be restoring a tumor restrictive stroma by normalizing extracellular matrix turnover is a strong asset in future clinical cancer research.
Nordic Bioscience's assays and services are research use only products and services and do not qualify for medical or diagnostic purposes.
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