PhD defence L.F. (Lisanne) van Dessel

From recent genomic analyses we know that metastatic prostate cancer (mPCa) has a highly complex genomic landscape and that only few distinctive characteristics recur, like androgen receptor (AR) alterations. This challenges our understanding of the biology of mPCa and of what alterations might guide treatment decisions. In this thesis I unraveled the genomic landscape of mPCa using whole-genome sequencing on a large patient cohort. We identified several distinct genomic clusters looking at specific genomic events or so-called ‘genomic scars’, that include patients that may be eligible for targeted therapy. In the future, this might guide researchers and clinicians to set up clinical trials to personalize cancer treatment. Next to better understanding the biology of the disease, this thesis focused on new blood-based biomarkers to further optimize treatment selection and evaluation.

This research is the first step to transit from metastatic biopsies, that only reflect a spatial and temporal snapshot of tumor heterogeneity, to liquid biopsies, that enables the study of cancer biology over time. For this I optimized the preanalytical conditions and I demonstrated the potential applications of liquid biopsies in mPCa. The assessment of genomic aberrations in circulating tumor DNA can potentially predict therapy response and detect mechanisms of resistance. Circulating tumor cells cannot only be enumerated as prognosticator in mPCa, but can also be used to culture ex vivo thereby providing novel disease models for mPCa and to predict therapy response. Furthermore, I demonstrated the clinical relevance of significant levels of 11-ketotestosterone in mPCa, a circulating steroid that is a potent AR agonist.

Due to corona, the PhD defences do not take place publicly in the usual way in the Senate Hall or in the Professor Andries Querido Room. The candidates will defend their dissertation either in a small group or online.