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). The increased collagen production and crosslinking, as well as altered degradation of the collagenous matrix result in loss of tissue organization and cellular behavior, release of growth factors, and in generation of cryptic sites on collagens with potent signaling activity. All these collagen alterations drive disease progression, immune suppression and affect treatment response. Moreover these ECM 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 Protein fingerprint technology. By quantifying 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.

The Scar-in-a-Jar model and associated protein fingerprint biomarkers offer a simple translational in vitro tool to address CAF biology and the direct impact of therapeutic intervention, in particular related to ECM remodeling. LINK

 


Protein Fingerprint biomarkers measured in serum are associated with disease activity. Evidence supports that changes in Protein Fingerprint biomarkers towards normalization are indicative of response and/or maintenance of no evidence of disease whereas increases in Protein Fingerprint biomarkers may be indicative of progression even prior to clinical manifestation. Understanding how therapies may potentially be restoring a tumor restrictive stroma by normalizing ECM turnover is a strong asset in future clinical cancer research.

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

Are you interested in learning more about Nordic Bioscience?
Enter your information in the form and a representative will contact you shortly.

By submitting this form you agree to our terms and conditions.

We use cookies on our site to enable essential services and functionalities, and collect data in regards to visitor information. This is done in order to provide the best possible experience for the visitor. Cookie policy Privacy statement