Blood-based marker opens up perspectives for cancer diagnostics

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Metastatic prostate cancer is currently associated with high morbidity and mortality rates. In addition, patients respond very differently to standard treatments such as hormone therapy or radiation therapy. Reliable markers that can be used to predict aggressive tumor progression and treatment success at an early stage are still largely lacking.

A research team led by Prof. Anna Dubrovska and Dr. Ielizaveta Gorodetska from OncoRay—National Center for Radiation Research in Oncology has now identified a biomarker that can be measured in the blood.

Prostate cancer is the most common type of cancer in men in Germany, with approximately 65,000 new cases per year, and the second leading cause of cancer death in men. If detected early, the prospects for successful treatment are good. In later stages, however, the cancer can spread. It then grows beyond the prostate into surrounding tissue or forms secondary tumors, known as metastases.

Building on earlier biomarker research

Dubrovska, who heads the Biomarkers for Individualized Radiotherapy working group at OncoRay, which is jointly supported by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR), the University Hospital Carl Gustav Carus Dresden (UKDD), and the Medical Faculty of TU Dresden, has already demonstrated in previous work that selected genes are suitable as biomarkers for prostate cancer.

In a study published in Journal of Experimental & Clinical Cancer Research , the team identified MMP11 (matrix metalloproteinase 11) as a promising protein biomarker detectable in blood plasma and therefore suitable for use in a blood test.

Dubrovska’s team worked with aldehyde dehydrogenases (ALDH) ALDH1A1 and ALDH1A3. These are enzymes that play an important role in the metabolism of humans and other living organisms.

Their earlier research showed that ALDH genes regulate the survival of tumor cells in the bloodstream and metastatic spread, thereby influencing resistance to radiation therapy and the formation of bone metastases. The researchers thus demonstrated that the genes can serve as potential biomarkers for disease progression in patients with prostate cancer.

How the signaling pathway drives disease

Gorodetska, who characterized the underlying ALDH1A1/MMP11 signaling pathway in detail, demonstrated that these ALDH proteins regulate another signaling protein, transforming growth factor beta 1 (TGFB1).

This, in turn, controls the production of other targets, including MMP11. This molecular signaling cascade plays a key role in making tumor cells more aggressive and invasive. The central finding of the study is the identification of MMP11 as a powerful biomarker. Analyses of multiple patient datasets show that high MMP11 gene expression is closely associated with advanced and high-risk prostate cancer.

Toward a blood test for aggressiveness

In addition, the team was able to confirm these findings by directly measuring MMP11 protein levels in the blood plasma of prostate cancer patients: the results show that elevated MMP11 concentrations in the blood are a potential marker for metastasis and a less favorable prognosis in patients with metastatic prostate cancer who are treated with local radiation therapy.

This opens up the prospect of a minimally invasive blood test that could help detect aggressive disease progression at an early stage, make more targeted therapy decisions, and monitor treatment success in real time.

“Our data show that MMP11 is not only a biologically relevant driver of tumor aggressiveness, but could also be a clinically useful marker,” explains Dubrovska.

“In the long term, such a blood test could help to treat patients more individually and avoid over- or under-treatment. Our results, therefore, represent an important milestone on the way to more precise, personalized, and patient-friendly diagnosis and treatment strategies for prostate cancer.”

Next steps toward clinical use

However, the path to clinical application is challenging. The researchers expect that the development of a clinically applicable test will take several years, as is the case with comparable biomarkers. Nevertheless, the current results mark an important milestone on the road to innovative, personalized diagnostic procedures in oncology.

An important next step has already been taken: in cooperation with the Polish Maria Sklodowska-Curie National Research Institute of Oncology, MMP11 is now being further validated across several independent liquid biopsy cohorts in Germany and Poland.