Metastasis heterogeneities provide possibilities for personalized therapy of patients with aggressive prostate cancer

Prostate cancer (PC) behavior ranges from harmless to lethal. Metastatic PC is treated by castration therapy followed by add-on therapies for castration-resistance. Therapy responses are heterogeneous and short-lived.

The overall goal of our translational research team is to improve treatment of metastatic PC by taking metastasis heterogeneities into consideration, for stratifying patients into best therapeutic option and for developing novel therapeutics.

Specific aims are to 1) explore molecular heterogeneities of clinical bone metastases in relation to patient outcome, with focus on the therapy-predictive value of the transcriptomic metastasis subtypes MetA-C, recently described and verified by us, and 2) identify molecular mechanisms behind MetA-C and functionally evaluate those, in order to discover novel subtype-specific therapeutic targets.

The project builds upon; 1) single cell RNA sequencing and histopathology to explore metastatic heterogeneities including MetA-C (year 1-3), 2) method developments for classifying MetA-C based on liquid biopsy analysis (CTCs, ctDNA, plasma) (year 1), enabling analysis of MetA-C in clinical (biobank) samples (yrs. 1-3), 3) integrated genetic and epigenetic analysis in relation to the MetA-C subtypes (year 1) and 4) functional exploration of possible mechanisms behind the MetA-C subtypes in experimental model systems (yrs. 2-3).

Ultimately, clinical intervention trials will translate our results into the clinic in the near future.