Novel targets and clinically relevant models for ovarian cancer

Despite an initial good response to platinum-based chemotherapy, most patients with ovarian cancer will suffer from a platinum-resistant relapse. Mechanisms behind this resistance and how to overcome it are still largely unknown. In this thesis we generated insight in the role of a DNA damage repair route and an immune reactive route in relation to response to platinum-based chemotherapy. It was found that targeting DNA repair routes will not always increase sensitivity towards chemotherapy and therefore targeting of this route should be performed with care. Although the function of the selective expression of immune reactive proteins on ovarian cancer is still unknown, they could be a target for tumor specific therapy. Furthermore, by implanting human ovarian tumor tissue into immune deficient mice, we established a new preclinical model, so-called patient-derived xenograft (PDX). This model retains most of its original characteristics such as protein expression and genomic instability. Also, by administrating fluorescent tracers, imaging of therapeutic targets expressed on the tumor was possible in this model. Therefore we conclude that the PDX model is a reliable and representative model for the testing of new drugs and studying resistance mechanisms in a preclinical setting of ovarian cancer