[How to manage patients with CRPC?].

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Prostate cancer progression is often driven by androgen receptor (AR) activity, even at castrate androgen levels.
• Several novel therapeutic agents, including enzalutamide, abiraterone, sipuleucel-T, and cabazitaxel, have demonstrated survival benefits in randomized phase 3 trials.
• Denosumab has shown efficacy in delaying skeletal-related events.

Purpose of the Study:

• To review the current landscape of prostate cancer treatment options.
• To discuss the challenges clinicians face in sequencing multiple treatment modalities.
• To explore potential mechanisms of resistance to novel hormone therapies.

Main Methods:

• Review of randomized phase 3 clinical trials for prostate cancer therapeutics.
• Analysis of treatment outcomes and survival benefits.
• Discussion of emerging resistance mechanisms, including AR splice variants.

Main Results:

• Multiple agents targeting the androgen axis, immune system, and chemotherapy have improved survival.
• Denosumab effectively manages skeletal complications.
• The complexity of treatment sequencing poses a clinical challenge.

Conclusions:

• The availability of diverse treatment options necessitates careful clinical decision-making and strategic sequencing.
• Constitutively active AR splice variants (AR-Vs) are implicated as a key mechanism driving resistance to advanced prostate cancer therapies.
• Understanding resistance mechanisms is crucial for optimizing treatment strategies in advanced prostate cancer.