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Brain metastasis of prostate cancer with selected intratumoral areas (pink and white circles) for undergoing molecular analyses. Credit: Antonio Rodriguez, Dept. of Pathology and DBMR |
Researchers at the University of Bern and University Hospital Bern have achieved a breakthrough in a particularly aggressive form of prostate cancer. In tissue samples from advanced brain metastases, they were able to establish the genetic profile of the cancer cells. These findings show for the first time that affected patients could benefit from target treatment, from which they have so far not been eligible.
Around 6,600 men are diagnosed with prostate cancer in Switzerland every year. It is the second most common cause of cancer-related death in men after lung cancer. Dangerous are advanced stages in which cancer cells have spread to other organs and form so-called metastases. However, unlike other cancers such as breast or lung cancer, the extremely dangerous metastases in the brain are very rare in prostate cancer. Only 1.5 percent of advanced cases have been diagnosed as brain metastatic prostate cancer (PCBM), according to a 2020 review study. As a result, PCBM cases have been poorly studied.
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Prof. Mark A. Rubin, Department for BioMedical Research and Bern Center for Precision Medicine, University of Bern and Inselspital, University Hospital Bern. Credit: Vera Knöpfel, University of Bern |
Alterations in the repair mechanism of cancer cells
In cancer cells, the cells' repair mechanisms are altered in such a way that they can no longer patch up certain damage in the genetic strand and therefore proliferate uncontrollably. In metastatic cells, an alternative repair mechanism steps into the breach, allowing the cancer cells to thrive. However, drugs known as PARP inhibitors specifically block this alternative repair mechanism and lead to the death of the cancer cells. However, this only works if the changes in the dangerous cells show a certain pattern in the primary repair mechanism.
In their study, the researchers examined prostate cancer brain metastases from 51 PCMB patients obtained from hospitals throughout Switzerland and from a partner institution in the USA. The analysis showed that alterations in the primary DNA repair mechanism were detected in all tested samples with brain-metastasizing prostate cancer cells. In about 20 percent of the patients studied, the researchers detected the exact genetic pattern in which, according to a study published in 2020, administration of PARP inhibitors significantly increased survival rates in those affected. "One in five patients with brain metastatic prostate cancer could therefore benefit from therapy with these targeted drugs", says Mark A. Rubin.
Prime example of precision oncology
At the same time, genomic analysis of brain metastases and comparison with other cancers opens new doors for basic research. "If we understand why there are fewer brain metastases in prostate cancer compared to other tumor types, we can learn in the future what changes in the cells make them malignant", explains Mark A. Rubin.
The work is also seen as a prime example of precision oncology in which treatment concepts are increasingly tailored to the specific patient. According to this approach, information on genetic profile of tumor cells of each individual patient is used to design a treatment using drugs that would target the specific alterations observed.
The study was supported, among others, by the Swiss Personalized Health Network (SPHN), the Swiss Cancer League, and in part by the Prostate Cancer Foundation, the U.S. National Institutes of Health (NIH), and the Prof. Dr. Max Cloëtta Foundation.
Source/Credit: University of Bern
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