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

ABSTRACT

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.

KEYWORDS:

• Personalized treatment
• pharmacogenetics
• drug interactions
• metastasis
• immunotherapy; prostate cancer

Article highlights

• The identification of drivers of drug resistance and insights into tumor genomics have paved the way for the introduction of tailored therapies in prostate cancer.

• Treatment resistance mechanisms and promising approaches to target actionable mutations are presented.

• The expanding armamentarium of treatment options in metastatic and non-metastatic CRPC requires physicians to take predictive clinical parameters, pharmacogenetics and drug interaction profiles, as well as compound-associated molecular biomarkers into consideration.

• Further comparative analysis of oncologic efficacy of eligible compounds, evaluation of drug toxicities and drug–drug interactions as well as identification of predictive biomarkers for compound selection is needed.

Declaration of interest

S Rausch has received honoraria from Pfizer Pharma, Astellas and Bayer Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.