Ex vivo tumor culture systems for functional drug testing and therapy response prediction.

Optimal patient stratification is of utmost importance in the era of personalized medicine. Prediction of individual treatment responses by functional ex vivo assays requires model systems derived from viable tumor samples, which should closely resemble in vivo tumor characteristics and microenvironment. This review discusses a broad spectrum of model systems, ranging from classic 2D monolayer culture techniques to more experimental 'cancer-on-chip' procedures. We mainly focus on organotypic tumor slices that take tumor heterogeneity and tumor-stromal interactions into account. These 3D model systems can be exploited for patient selection as well as for fundamental research. Selection of the right model system for each specific research endeavor is crucial and requires careful balancing of the pros and cons of each technology.

PARP inhibitors: the journey from research hypothesis to clinical approval.

Cancer puts an increasing burden on our healthcare system and is a major cause of death. Therefore, novel approaches are required to improve cancer treatment. Cancer cells have several hallmarks that could be therapeutically targeted. Importantly, every tumor has a different combination of aberrations affecting the different hallmarks. This review focuses on targeting one of these hallmarks, the DNA damage response (DDR). DDR defects can not only cause cancer, but they can also be exploited therapeutically. This plays an important role even in 'classical' (DNA damaging) chemotherapy and radiotherapy, but more precise targeting of specific defects is expected to increase treatment efficacy and decrease normal tissue toxicity. Poly-(ADP-ribose) polymerase (PARP) inhibitors are the first clinical example of such synthetic lethality in tumors having specific DDR defects. They are currently under investigation as DDR-targeting anticancer drugs and they progress quickly in clinical trials.