The detection of biomarkers from body fluids (so-called liquid biopsy) is playing an increasingly important role in the personalized treatment of tumor diseases. In contrast to obtaining a conventional tissue sample from the tumor, liquid biopsy can be performed non-invasively at any time by simply taking a blood sample. Tumor-specific altered genetic information (DNA) or proteins released from the tumor cells into the blood can be detected with high accuracy and their concentration measured. This makes liquid biopsy an excellent tool for monitoring the progression of cancer, assessing the effectiveness of treatment and detecting relapse at an early stage after treatment.

In subproject P5, we will focus on the analysis of circulating tumor DNA (ctDNA) from plasma samples using digital PCR (dPCR) and targeted next generation sequencing (NGS) for tumor-specific mutations derived from patients with curatively intended treatment of colorectal cancer (CRC). The project is divided into two phases.

• Phase 1 will initially include patients who cannot be treated curatively. We will study plasma samples from patients with CRC aged up to 50 years obtained at the time of diagnosis and prior to initiation of treatment OR at the time of relapse after treatment. In addition, we will analyze healthy control plasma samples (P9) and samples from mouse models (P3) in an analogous manner.
• In Phase 2, we will focus on patients with curatively intended treatment and analyze plasma samples from CRC patients at the following time points: at diagnosis before treatment initiation; after treatment completion; and at the time of relapse. In addition, we will analyze healthy controls.

It is expected that the combination of P5 ctDNA analysis with metabolomic (P3), microbiomic and epigenomic (P4) and proteomic (P6) biomarkers will improve the detection of CRC-specific patterns in CRC patients at increased risk of relapse or actual relapse when these markers are integrated into a multi-marker panel (P7, P8). P5 investigates two potential technologies for detecting tumor mutations in círculating DNA from tumor cells (ctDNA).