Pathomechanisms of disease-progression in urothelial and prostate cancer

The concept of (clonal) evolution has been used in cancer research for decades. Recent technological progress made it possible to further elucidate cancer populations on a unprecedented resolution. Using these new technologies, we are able to depict the evolutionary pattern of an individual cancer. Delineation of these patterns is crucial for understanding the pathomechanisms of therapy-resistance and disease-progression, especially in the era of personalized medicine.
In this PhD-studies we use two different approaches. First, we analyse different cancer manifestations within the same patients. This way, we are able to understand the clonal relationship between the different tumorsites.
In case of the first publication, we took samples from different locations and different time points from a single patient. We could show an association of an early cancer onset with a previously unknown viral mutation in a Polyomavirus B.K. strain. A virus which’s oncogenic potential is controversially discussed in the literature.
With our second publication we were able to depict the clonal relationship of different tumor locations within the same prostate. An understanding of this relationship might identify clinically relevant clones. This is of special importance in prostate cancer due to its multifocality. While doing this, we additionally validated the use of morphological assessment to determine a cancer cell’s ploidy status.
Besides understanding a tumor’s escape routes, another pillar of successful personalized therapy is the correct assessment of patients before therapy. The use of quality biomarkers is crucial in this context.
ARID1A mutational status has shown to be of predictive value of therapy response to BCG therapy in patients with non-muscleinvasive bladder cancer. So far, the evaluation of ARID1A status has been done on tissue samples. In our last publication we were able to show that analysing ARID1A in urine using immune-cytology is feasible. Therefore, we established a protocol to acquire this information in a non-invasive way.