PhD defence G. (Gido) Snaterse

Prostate cancer (PC) is one of the most common forms of cancer in men. Steroid hormones, and androgens in particular, are important activators of the androgen receptor (AR), which causes PC  cells to grow. The actions of these hormones in advanced PC are not fully understood yet. 

The studies in this thesis investigate the metabolism of steroid hormones in PC cells, their presence in castration-resistant PC (CRPC) patients and their interactions with the AR. First, an overview of steroid concentrations in healthy men and PC patients in literature is provided. Some of these steroids, such as testosterone, can directly activate the AR, while others must first be converted into active androgens by PC cells. However, this thesis also shows that this process is limited to steroids downstream of the enzyme CYP17A1, as PC cells effectively lack this. 

This thesis shows that samples obtained in non-standard blood tubes can be utilized to measure steroid hormones in the circulation. By measuring steroids in CRPC patients, we show that the recently discovered 11-ketotestosterone is the most abundant active androgen in the blood of these patients, and may therefore play an important role in disease progression. Furthermore, the data shows that mutations in AR, occurring in approximately 20% of CRPC patient, drastically affect the binding of various steroids to the AR. Of note, dexamethasone may be a suitable alternative to prednisone in patients carrying specific AR mutations. Finally, this thesis identifies a potential new mechanism through which salt intake affects cortisol metabolism.

The PhD defences will not take place publicly in the usual way. A live stream link has been provided to candidate. The ceremony will begin exactly at 13:00.