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Colorectal liver metastases: DNA damage could predict prognosis and treatment response

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(Vienna, 06 June 2018) In a new study, scientists from the Division of General Surgery within the Department of Surgery of the Comprehensive Cancer Centre (CCC), MedUni Vienna/Vienna General Hospital, showed that double-strand DNA breaks can predict disease progression and treatment response in metastatic bowel cancer (colorectal cancer, CRC). In a translational study, they were able to show that this type of DNA damage is associated with a poorer prognosis, thereby contradicting preclinical data. The study was conducted inter alia within the framework of the Ludwig Boltzmann Institute Applied Diagnostics (lbi:ad) and has now been published in leading journal "Theranostics".

Bowel cancer is the third commonest form of cancer and the fourth commonest cause of cancer deaths in both men and women worldwide. Half of sufferers develop liver metastases over time. Currently approximately 30% of these patients can be cured. It is therefore all the more urgent to identify new biomarkers to improve prediction of prognosis and treatment response.

Importance of translational studies
In the past, studies into cell lines and in animal models have shown that strand breaks in the DNA of cancer cells lead to the production of Type I interferon. This is a messenger substance essential for the induction of cytotoxic T lymphocytes. These immune defence cells target cancer cells, thus improving the chances of overcoming the disease.

Says lead author Johannes Längle, Division of General Surgery of the Department of Surgery and member of the CCC: "Our study contradicts the results of preclinical studies and shows that DNA damage has a negative impact upon relapse-free survival and overall survival. It even indicates that patients with colorectal liver metastases who exhibit a high degree of DNA damage constitute a high-risk group."

Co-lead investigator Dietmar Pils, Institute of Clinical Biometrics of the Centre for Medical Statistics, Informatics and Intelligent Systems, likewise a member of the CCC, adds: "Our study highlights the importance of translating data obtained in preclinical studies to a clinically applied situation in humans. Of course, it is necessary to check this translation in larger cohorts, in different stages of the disease and for different types of cancer."

Better markers for more precise medicine
Lead investigator, Michael Bergmann, Division of General Surgery within the Department of Surgery and member of the CCC, regards the study as an important contribution to the advancement of precision medicine, since markers for these strand breaks could serve as prognostic and predictive biomarkers for treatment. He says: "Just recently a Positron Emission Tomography (PET) marker was developed for DNA damage. It was used for the ongoing evaluation of treatment response and/or prediction of clinical prognosis."

Service: Theranostics
"DNA damage predicts prognosis and treatment response in colorectal liver metastases superior to immunogenic cell death and T cells.”
Laengle J, Stift J, Bilecz A, Wolf B, Beer A, Hegedus B, Stremitzer S, Starlinger P, Tamandl D, Pils D, Bergmann M. Theranostics 2018; 8(12):3198-3213. doi:10.7150/thno.24699.