Xenograft and Organoid models

Patient-derived xenograft (PDX) and organoid (PD(X)O) models of prostate cancer

Current drug selection is predominantly based on 2D cell lines. The high failure rate of drugs in clinical trials is thought to be, at least in part, caused by the use of preclinical models that inadequately reflect the clinical disease. Over many years, we have established a diverse panel of prostate cancer PDXs that spans a wide range of disease stages. We now focus on the generation of 3D organoids, both from these PDXs and directly from prostate cancer patients. We will apply these near-patient in vitro models in large scale (image based) drug screens to select novel compounds that interfere with tumor growth.  (Wytske van Weerden)

Immune therapy: MuCaP mouse model 

Prostate cancer has so far poorly responded to immune therapy with immune checkpoint inhibitors, which has been attributed to low T cell infiltration and poor T cell activation. We have established a PCa Pten-knockout mouse model consisting of  four syngeneic lines, which link indolent tumors to be strongly infiltrated with effector cytotoxic CD8+ T-cells, whereas aggressive tumors were poorly infiltrated and lacked a CD8+ T-cell signature. We aim to select sensitization treatments to improve response of PCa to immunotherapy.  (Wytske van Weerden)

Imaging tools for 3D cancer model systems

Advanced 3D culture systems are being generated to better represent the in vivo cancer. To make optimal use of these 3D model systems, we develop quantitative fluorescent imaging approaches and implement them in the development in prostate cancer model systems for drug discovery and metastasis. (Martin van Royen)

People working on the project