Early biomarkers for androgen deprivation treatment failure

Approximately 1/3 of the 5000 men yearly diagnosed with prostate cancer in Norway are not candidates for curative treatment. Androgens are essential hormones for the growth and differentiation of the prostate and androgen deprivation therapy (ADT: castration, LHRH agonists and antagonists, anti-androgens) has been the standard of care for this group of patients for more than sixty years. Although ADT in general is an effective treatment option for prostate cancer patients, castration-resistant prostate cancer (CRPC) inevitably develops over time.

Prostate cancer is a clinically heterogeneous disease. Over the past decade, researchers have begun to unravel some of the molecular heterogeneity that contributes to these varying clinical phenotypes.  However, none of the molecular signatures identified have yet been implemented in the clinic.

We plan to analyse the transcriptome and proteome in cancer tissue collected from patients that have undergone radical prostatectomy and later received ADT treatment, as well as patients that have not been treated with ADT. The results from these analyses will be merged with clinical data and information about the treatment effect to identify signatures and models that can be used in predicting the effect of androgen deprivation therapy.

The aim is to develop a model that can be used in the treatment decision process in a way that patients who are expected to respond well to hormone therapy are given ADT, while others are given different treatment options. This study could also give us a better molecular understanding of why some patients are good responders and others not. This knowledge might be useful in the development of new medications and treatment regimens.

Project members: Peder Rustøen Braadland, Shivanthe Sivanesan and Håkon Ramberg