Project 466863

Esophageal adenocarcinoma (EAC) is characterized by low survival rates and has had an increase in incidence in recent decades. Liquid biopsies from EAC patients have the potential to improve diagnosis and prognosis of this disease, by using circulating tumour DNA (ctDNA) and tumour-derived extracellular vesicle DNA (EV-DNA) in patient biofluids as biomarkers of disease progression. However, there is a limited understanding of the mechanisms of ctDNA and EV-DNA release from cancer cells. Particularly, how different treatments, such as chemotherapy or radiation, affect ctDNA and tumour-derived EV-DNA remains poorly understood. The aim of the present study is to use EAC patient samples to elucidate the impact of treatment and treatment response on ctDNA and EV-DNA kinetics and fragmentation. ctDNA and EV-DNA from EAC patient blood samples and from the supernatant of EAC patient-derived organoids treated with in vitro chemotherapy will be isolated. DNA level and fragment size will be compared and associated to different treatments, responses to treatment, development of metastatic disease, and time points of sample collection. This project has the potential to clarify the mechanisms of DNA release from cancer cells, and to identify molecular alterations that could be used for non-invasive diagnosis, prognosis, and detection of treatment resistance in cancer patients.