Dr. Johannes Längle
MedUni Wien RESEARCHER OF THE MONTH March 2019
Colorectal liver metastases: DNA damage could predict prognosis and response to therapy
Colorectal cancer (CRC) is the third most common type of cancer and the fourth leading cause of cancer mortality in women and men worldwide . Half of those patients affected with CRC will develop liver metastases (CLM) over time . Currently only 30% of these patients can be cured . This calls for the urgent need to develop new markers to better predict prognosis and treatment response.
Studies on cell lines and animal models revealed that DNA damage of tumor cells can lead to type I interferon (IFN) induction . Type I IFN is a signaling molecule, which is essential for the induction of cytotoxic T lymphocytes . These immune cells are further capable to target the tumor cells and thereby improving the chances to overcoming the disease .
Our work disproves the results of the preclinical studies and demonstrates that DNA damage has a negative impact on recurrence-free and overall survival . She even points out that patients with CLM, which show high DNA damage, represent a high-risk group. This study highlights the importance of translating data obtained in preclinical studies to a clinically setting. Nevertheless, this translation should still be examined in larger cohorts, as well as in different disease stages and cancers.
This study makes a significant contribution to the advancement of precision medicine, as markers for these strand breaks could serve as prognostic and/or predictive biomarker for therapy treatment. Recently, a positron emission tomography (PET) marker for DNA damage has been developed , which could serve for the evaluation of treatment response and/or prediction of clinical prognosis during the course of the disease.
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