Humoral cancer detection: Towards improved diagnostics of malignancies using bodily fluids

Cancer has a major impact on health and is a leading cause of death in developed countries. While advancements in diagnostics and treatment have improved the overall prognosis, for many types of cancer this is not the case. One major reason is the inability to timely detect the tumor or to accurately trace tumor activity. Many cancers are diagnosed at an advanced stage, when curation is not feasible anymore. Reliable and more sensitive means for early cancer detection, would ultimately improve mortality rates. Furthermore, current diagnostic modalities that monitor tumor activity before, during or after anti-cancer therapies lack sensitivity. The use of liquid biopsies, which can detect tumor-specific molecules in bodily fluids, provides a non-invasive approach for real-time cancer diagnostics. These tests offer both quantitative and qualitative data about tumor activity, making them a promising tool for monitoring cancer. Circulating tumor DNA (ctDNA) is the most studied substrate and these blood-based liquid biopsies are currently being implemented in clinical care. A still relatively unexplored medium for obtaining liquid biopsies is urine, which has many potential advantages compared to blood sampling. This thesis explores the potential of ctDNA in blood and urine to detect colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). Part 1 of this thesis evaluates blood ctDNA for the purpose of cancer detection but also other clinical modalities such as prognosticating and monitoring of therapy response. Part 2 explores the pre-analytical variables that are required for a sensitive detection of ctDNA in urine. Finally in part 3, evidence is shown that detection of cancer DNA in urine is feasible in cancers of different subtypes.