Prostate cancer is the most prevalent malignant disease in men. While localized disease can be cured, metastatic disease cannot Virtually, all metastatic prostate cancers respond to lowering serum testosterone levels. However, eventually the disease will reactivate despite ongoing testosterone suppression. Our group explores gene regulation in prostate cancer which is predominantly dictated by the androgen receptor. Moreover, prostate cancer develops through distinct stages, and there is emerging evidence that components of the tumor microenvironment play an important role in driving progression. We have a special interest in the role of the innate immune system in prostate cancer development. All our studies are aimed to better understand the mechanisms behind prostate cancer progression and sensitivity to treatments, with the ultimate goal to better understand hormonal signaling and therapy resistance in cancer. Ultimately, these new insights might contribute to more personalized treatments, the identification of novel therapeutic options and minimizing over-treatment
Genome-wide Androgen Receptor profiling in prostate cancer
We are currently performing two Phase II clinical trials, in which patients receive AR-targeting Enzalutamide treatment in the neo-adjuvant (DARANA; Dynamics of Androgen Receptor Genomics and Transcriptomics After Neoadjuvant Androgen Ablation. NCT03297385) and metastatic (PRESTO; Predicting Response to Enzalutamide as a Second Line Treatment for Metastasized Castration Resistant Prostate Cancer Patients: a biomarker design study) setting, aimed to elucidate the cellular plasticity of AR functions in prostate cancer and treatment resistance, and to better understand the impact of DNA mutations on transcriptional regulation in cancer.
The role of the innate immune system in prostate cancer development
The innate immune system and especially its dominant representatives, the macrophages, play a pivotal role in prostate cancer development, which is reflected by a relation between disease recurrence after prostatectomy and to the abundance of macrophages in the tumor microenvironment. Macrophages are plastic cells that can exert multiple functions depending on their phenotype. Through single cell sequencing of isolated macrophages from the tumor microenvironment, we identified three different phenotypes of cancer associated macrophages. Moreover, we discovered that the androgen receptor in macrophages is functional and affect the plasticity of these cells. With that, macrophages are targeted by antihomonal manipulations. We now study the prostate cancer cell bound factors that dictate sensitivity to macrophage cell killing.