Treatment and resistance mechanisms in castration-resistant prostate cancer: new implications for clinical decision making?

Introduction: The armamentarium of treatment options in metastatic and non-metastatic CRPC is rapidly evolving. However, the question of how individual treatment decisions should be balanced by available predictive clinical parameters, pharmacogenetic and drug interaction profiles, or compound-associated molecular biomarkers is a major challenge for clinical practice. Areas covered: We discuss treatment and resistance mechanisms in PC with regard to their association to drug efficacy and tolerability. Current efforts of combination treatment and putative predictive biomarkers of available and upcoming compounds are highlighted with regard to their implication on clinical decision-making. Expert opinion: Several treatment approaches are delineated, where identification of resistance mechanisms in CRPC may guide treatment selection. To date, most of these candidate biomarkers will however be found only in a small subset of patients. While current approaches of combination treatment in CRPC are proving synergistic effects on cancer biology, higher complexity with regard to biomarker analysis and interaction profiles of the respective compounds may be expected. Among other aspects of personalized treatment, consideration of drug-drug interaction and pharmacogenetics is an underrepresented issue. However, the non-metastatic castration resistant prostate cancer situation may be an example for treatment selection based on drug interaction profiles in the future.