We focus on the behavior of castration-resistant prostate cancer (CRPC) with the aim to identify new therapeutic targets. We also investigate the direct role of androgen deprivation therapy (ADT) in the differentiation of the highly metastatic phenotype associated with CRPC.
Prostate cancer is initially dependent on circulating androgens, and therefore ADT is the standard treatment for advanced disease. The effect is often good, but tumors inevitably relapse in a CRPC form, which is often fatal. CRPC often still expresses androgen receptor (AR) and mechanisms for its ability to grow in castrate testosterone levels includes increased AR expression or sensitivity together with an acquired capacity of de novo steroid synthesis or conversion of steroid precursors to support AR with sufficient ligand for transcriptional activation.
Normally, testosterone induces prostate epithelial cell differentiation and regulates prostate vasculature. We and others have shown that ADT induces de-differentiation not only in androgen-dependent cells, but also in CRPC cells. Several pro-metastatic proteins are induced by ADT. The nature of these changes and their dependence on intratumoral androgens, possible environmental specificity, role in metastasis and drug resistance, and potential as future drug targets, are all subjects for experimental projects in our group.
In a more clinically related part of our research we study the effect of ADT on anti-angiogenic cytotoxic treatment strategies in animal models. We also develop alpha-radio immunotherapy specifically for bone metastasis of prostate cancer in collaboration with Drs. Jacobsson and Bäck at the department of Radiation Physics.
We use molecular and cellular techniques to study ADT-induced changes in both in vitro and in vivo systems including mouse xenograft models of human prostate cancer. Further, we collect human samples from different stages in disease progression for molecular analysis.
Jan-Erik Damber, MD, PhD, Professor
Karin Welén, PhD
Andreas Josefsson, MD, PhD
Anna Nordin, PhD student
Malin Hagberg, PhD student
Åsa Jellvert, MD, PhD student
Anna Linder, PhD student
Karin Larsson, MSc, Molecular biologist