Cancer Initiation and Progression

Metastasis of prostate cancer to liver and bone (in vivo and in vitro)     

 Disseminated prostate cancer is dominated by skeletal metastasis. With current life-extending therapies, increased morbidity due to visceral (liver) metastatic disease is urging for dedicated interventions.

We aim to identify and characterize circulating tumor cells that invade and colonize healthy liver and bone micro-tissues to find new molecular targets for metastasis-specific treatment. For this purpose, we use a spontaneous metastasis model of prostate cancer with (micro)metastatic lesions in lymph node, lung, liver and bone of immune-deficient mice, mimicking the natural course of disseminated disease in patients. We currently work to replace this animal model by a humanised 3D cancer-on-chip in vitro system with healthy human liver and bone micro-tissues. (Wytske van Weerden)

Long noncoding and circRNAs as biomarkers and functional transcripts in prostate cancer

The largest and most diverse groups of RNAs include the linear and circular long noncoding RNAs. With 50,000 – 160,000 different species that do not encode for proteins, their function is poorly understood. From RNA-seq data we identified PCa-associated transcripts and explore their role in PCa initiation and progression. (Guido Jenster)

(Fusion) genes and pathways responsible for prostate cancer initiation and progression

Gene rearrangements are common driver event in PCa. Particularly the TMPRSS2-ERG fusion and AR amplification and AR variant expression are frequently observed. However, also rare and private driver gene mutations are identified from Next Generation sequencing data. The role of these genes and pathways is being studied with respect to the different cancer hallmarks. (Guido Jenster)

Ribosomal RNA methylation

Epitranscriptomics, the study of RNA modifications, is an exciting new research field with strong potential for clinical utility. Among the many different modifications found in RNA, RNA methylation is most abundant and diverse and commonly altered in cancer. I study how alterations in the methylation signatures of ribosomal RNA and the underlying snoRNA-guided molecular machinery affect the tumorigenesis and progression of prostate cancer. A special focus of my research is how such changes can be used to develop novel biomarkers and therapeutics for the management of (late stage) prostate cancer. (Elena Martens)

Key words: epitranscriptomics, ribosome, RNA methylation, Nm, 2’-O-methylation, snoRNA, biomarker, therapy

Unraveling androgen receptor function in prostate cancer

The androgen receptor (AR) signaling axis is the main target in prostate cancer, but is often also involved in therapy resistance. Unraveling the molecular mechanism of AR function using innovative quantitative imaging techniques will identify novel targets in the AR axis and enable the development of novel therapeutic approaches. (Martin van Royen)

PSMA-targeted peptide receptor radionuclide therapy (PRRT) of prostate cancer 

 Prostate Specific Membrane Antigen (PSMA) is an ideal target for imaging and therapy of prostate cancer using radiotracers. We aim to uncover the full therapeutic potential of PSMA-targeted tracers by selecting the most optimal tracer and radionuclide and enhance the tumor radiosensitivity while at the same time investigating new methods to protect healthy PSMA-expressing organs, such as salivary glands and kidneys, to prevent radiotoxicity. (Wytske van Weerden)

3D tissue architecture of prostate cancer

Little is known of the 3D microscopic composition of cancer. By developing and applying optical clearing approaches we improve insight in the 3D architecture of growth patterns and strongly enhance understanding of cancer behavior and important cancer related processes in clinical cancer samples and complex tumor models. (Martin van Royen)

Resistance mechanisms: CRPC, taxane resistance, radioresistance

The majority of patients encounter loss of responsiveness or are intrinsically resistant to the applied therapies, e.g. castration-resistant prostate cancer (CRPC) after hormonal therapy, taxane resistance upon treatment with docetaxel or cabazitaxel, and resistance to radiotherapy. We aim to identify the mechanisms of resistance using relevant preclinical models and to define and test treatment alternatives to overcome resistance. (Wytske van Weerden)

People working on the project