9. Detection of Circulating Tumor DNA in CRC Apoptotic or necrotic dying tumor cells are thought to release short DNA fragments into the bloodstream that contain tumor-specific genomic alterations. This cell free circulating tumor DNA (ctDNA) can be easily collected non-invasively via blood samples from CRC patients [36]. Recently, it was demonstrated that ctDNA analysis is a powerful tool to monitor development of drug resistance in patients undergoing therapy with EGFR inhibitors [37]. The authors could show that >95% of patients that originally responded to anti-EGFR therapy but subsequently relapsed developed mutations in genes involved in the mitogen-activated protein kinase pathway. Thus, ctDNA mutation analysis may become an effective biomarker in the management of CRC. However, before it can enter into clinical routine, further studies are needed on the source of ctDNA and the robustness of its analysis.