PhD defenceW. (Wenhao) Zhang

Prostate cancer (PCa) remains a heavy burden in current healthcare as it is the most common non-skin cancer and fifth leading cause of cancer-related death in males. Despite progress in understanding the biology of PCa and developing new drugs and therapeutic strategies, advanced stage PCa continues to be incurable and development of drug resistance remains a crucial issue. Extensive research has aimed to further understand PCa, including developing more reliable preclinical models, increasing treatment efficacy, selecting best patients for certain treatment regimen and predicting treatment response. The role of the DNA damage response (DDR) has drawn particular attention in recent years as an increasing number of PCa patients harboring DDR defect is being identified. These findings may have important implications for their treatment, since new DDR-targeting compounds show great potential for precision medicine. Furthermore, the recently discovered crosstalk between the DDR machinery and androgen receptor (AR) signaling opens a new array of possible strategies to enhance treatment efficacy. This thesis describes the development of novel 3D in vitro PCa models, analysis of DNA double-strands break (DSB) repair in PCa and how the DDR may impact PCa treatment. Preclinical research of PCa depends heavily on a limited number of conventional 2D cell lines. Although their homogeneity and ease of handling makes them valuable models for high-throughput experiments, lack of complex architecture and cell interaction makes them “unrepresentative’’ models and may lead to a failure when transitioning a new treatment from bench to clinic. To overcome this, two distinct methods to culture 3D PCa tumor in vitro are being discussed in this thesis.

The public defence will take place at the Prof. Andries Queridoroom, 3rd floor Education Center, Erasmus MC. The ceremony will begin exactly at 13.30 hrs. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.