# Emerging Therapeutic Strategies in Prostate Cancer: Targeted Approaches Using PARP Inhibition, PSMA-Directed Therapy, and Androgen Receptor Blockade with Olaparib, Lutetium (177Lu)Vipivotide Tetraxetan, and Abiraterone

## TL;DR

This review discusses new targeted treatments for advanced prostate cancer, including PARP inhibitors, PSMA-directed therapy, and androgen receptor blockers, and how they can be used effectively in clinical practice.

## Contribution

The paper provides a clinically focused overview of integrating PARP inhibition, PSMA-directed RLT, and ARPIs in advanced prostate cancer treatment.

## Key findings

- Olaparib benefits mCRPC patients with HRR mutations, especially BRCA1/2.
- PSMA-directed RLT improves survival in PSMA-positive mCRPC after AR pathway inhibition.
- Abiraterone remains a key therapy and can be combined with other agents for better outcomes.

## Abstract

Prostate cancer is one of the most common malignancies in men, and advanced or metastatic disease remains associated with substantial morbidity and mortality. Therapeutic progress in recent years has been driven by the introduction of targeted treatment strategies, notably poly (ADP-ribose) polymerase (PARP) inhibitors, prostate-specific membrane antigen (PSMA)–directed radioligand therapy (RLT), and androgen receptor pathway inhibitors (ARPIs). This review summarizes evidence from phase II and III clinical trials, meta-analyses, and real-world studies evaluating the efficacy, safety, and clinical integration of olaparib, lutetium (177Lu) vipivotide tetraxetan, and abiraterone in advanced prostate cancer. Emphasis is placed on the practical clinical application of these agents, including patient selection, treatment sequencing, and combination strategies. PARP inhibition with olaparib has demonstrated clear benefits in metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) mutations, particularly BRCA1/2 alterations. PSMA-directed RLT offers a survival advantage in PSMA-positive mCRPC following AR pathway inhibition, with distinct toxicity considerations that influence patient selection. Abiraterone remains a cornerstone therapy across disease stages and plays an important role both as monotherapy and as a combination partner. Emerging data suggest a potential synergy between PARP inhibitors and AR-targeted agents, while also highlighting the limitations of biomarker-unselected approaches. We conclude that the optimal use of PARP inhibitors, PSMA-targeted RLT, and ARPIs requires a personalized strategy guided by molecular profiling, functional imaging, prior treatment exposure, and safety considerations. This clinically focused overview aims to support evidence-based decision-making in an increasingly complex treatment landscape.