PhD defence M.K. (Manouk) Bos

Below is a brief summary of the dissertation:

Technical advances in molecular diagnostics over the past two decades have made it possible to map cancer DNA. As a result, we have gained insight into how changes in cancer DNA can contribute to how a cancer cell behaves in the body. An accumulation of changes in a cell's DNA can lead to the development of cancer in the first place; when a cell has acquired properties to divide uninhibitedly. Secondly, changes in cancer DNA can cause a cancer cell to escape mechanisms that try to destroy the cancer cell, such as our own immune system or anti-cancer treatments like chemotherapy, for example. This also means that cancer DNA changes over time, and due to anti-cancer treatments. The technique used to map DNA is also called sequence analysis. To collect tumour cells for genetic research, current practice involves a puncture or biopsy of the tumour. Nowadays, it is also possible to examine the DNA of cancer cells in the blood of the patient with cancer. This has advantages, e.g. blood sampling is usually less stressful for patients than punctures or biopsies. Also, the presence of circulating tumour DNA can provide information about the extent to which the cancer has spread through the body. In addition, there is evidence that DNA found in the blood better reflects all genetic abnormalities present compared to a single puncture or biopsy when a patient has multiple metastases. Currently, circulating tumour DNA is mainly looked at in research settings. Several applications of circulating tumour DNA are being explored in practice. For instance, circulating tumour DNA can be used to detect tumour genetic characteristics that make a tumour sensitive to a specific treatment. Circulating tumour DNA can also be used to measure whether there are any residual cancer cells present in the patient's body, for example after completing treatment. The overlapping goal of this is to tailor treatment even better to characteristics of both the tumour and the patient. This is also known as precision medicine.

The aim of the research described in this thesis is to contribute to the implementation of circulating tumour DNA as a test to improve the outcomes and quality of life of patients with cancer.