Projekt 6

IDENTIFICATION OF PREDICTIVE PROTEOMIC PROFILES IN PROSTATE CANCER BY USE OF A FUNCTIONAL EX VIVO ASSAY

Prostate carcinoma (PCa) is the most common tumor entity in men worldwide. One pillar of therapy is radiation therapy, but not all tumors respond equally well. Enhancing the radiation effect (radiation sensitization) while sparing normal tissue would therefore be useful. The radiation sensitivity of tumor cells is primarily determined by their ability to repair radiation-induced DNA double-strand breaks (DSB). In this context, DSB repair is subject to a specific hierarchy and occurs primarily via non-homologous endjoining (NHEJ), but also homologous recombination (HR). In tumor cells, this hierarchy is often disrupted by defects in HR or a shift in repair toward PARP1-dependent NHEJ. Such dysregulations can lead to increased radiosensitivity, but can also be exploited for targeted radiosensitization, for example by using specific inhibitors such as olaparib and/or ERG-USU (inhibitors of PARP and ERG, respectively) . Together with the cooperation partners from the Martini Clinic, it could be shown for the first time that a combination of olaparib treatment and radiation leads to an increased number of unrepaired DNA double-strand breaks and thus to a sensitization to radiation in approx. 30% of high-risk PCa. This implies that this could improve therapy for these patients. However, molecular markers that predict response do not yet exist. Mass spectrometry is a particularly suitable method for identifying such markers. Both individual marker proteins can be identified and characteristic profiles consisting of several proteins can be created in the case of tumor tissues.