ctDNA (circulating-tumor DNA) in prostate cancer patients

Prostate cancer is a common health problem among men worldwide. Advanced genetic engineering techniques have significantly expanded our understanding of the genetic basis of prostate cancer. Nevertheless, important questions regarding early diagnosis and characterization of the tumor genome remain open in patients with metastases or recurrent disease. Therefore, we have developed a new approach based on the whole genome sequencing technique of plasma DNA, which we named plasma-Seq, to study the genome of patients with cancer non-invasively, ie from a single blood sample. With this technique, also known as "liquid biopsy", it is possible, in contrast to tissue examinations, to obtain samples within a short period and to track response to a specific therapy. In the process, new genetic changes, which can be held responsible for a lack of response and thus a progression of the disease, can occur. Yet, on the other hand, these changes offer the opportunity to switch to a targeted, alternative therapy at an early stage. In blood samples from patients with prostate cancer, we have already been successful in detecting genetic alterations associated with advanced disease. We have already demonstrated that detection is possible, even if the tumor content is only a few percent of the plasma DNA. In this project, we would like to focus on castration-sensitive prostate cancer (CRPC). This is a highly variable clinical picture with differentiated and burdening symptoms. The clinical parameters used to estimate the prognosis have so far only shown a very limited valence; genetic markers have so far only rarely been investigated. In the course of our preliminary investigations, we were already able to isolate 189 plasma samples from 59 patients with metastatic prostate cancer. These samples are prepared by highly innovative techniques, e.g. "whole genome sequencing", in order to gain comprehensive insights into the spectrum of genetic changes under therapy and the associated tumor evolution. These results should be compared with the genetic material of the respective prostate tumors, which originate from previous operations. This highly comprehensive data, which will yield results on copy number changes, mutations, and gene expression, will allow analysis of signaling pathways of unprecedented resolution to increase the efficacy of targeted therapies in patients and minimize the burden of non-effective therapy side effects.