PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGETED THERAPIES IN THE TREATMENT OF PROSTATE CANCER: ADVANCES, EFFICACY, AND FUTURE DIRECTIONS

Abstract

One of the most common cancers to be identified in men globally, prostate cancer continues to be a significant source of cancer-related morbidity and mortality, especially in advanced stages [1,2]. Due to its significant increase in prostate cancer cells, particularly in high-grade, metastatic, and castration-resistant illness, while exhibiting little expression in normal tissues, prostate-specific membrane antigen (PSMA) has become a very intriguing molecular target [5,6]. Positron emission tomography (PET) imaging based on PSMA has greatly enhanced disease detection, staging precision, and patient selection for targeted therapy [8–11]. PSMA-targeted radioligand therapies, especially lutetium-177-labeled PSMA-617, have shown significant improvements in progression-free and overall survival in patients with metastatic castration-resistant prostate cancer, building on these diagnostic advancements. This has led to regulatory approvals and integration into clinical practice [12–15]. The therapeutic landscape is further expanded by alpha-emitting radioligands like actinium-225–PSMA and newly developed PSMA-directed immunotherapeutic strategies such antibody–drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor T-cell treatments [16–21]. Despite promising results, toxicity-related issues, tumor heterogeneity, resistance mechanisms, and appropriate patient selection persist [18,22]. This review offers a thorough summary of the biological justification for PSMA targeting, the available clinical data in favor of PSMA based imaging and therapeutic approaches, related drawbacks, and potential future directions for improving customized and multimodal prostate cancer treatment approaches.