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Therapeutic Advances in Metastatic Prostate Cancer: A Journey from Standard of Care to New Emerging Treatment

by Litterio, Giulio , Tătaru, Octavian Sabin , Cicchetti, Rossella , Ferro, Matteo , Marchioni, Michele , Giulioni, Carlo , Mascitti, Marco , Cafarelli, Angelo , Salzano, Gaetano , Basconi, Martina , Digiacomo, Alessio , Schips, Luigi , Orsini, Angelo

in Agonists / Androgens / Cancer therapies / Chemotherapy / Combination therapy / Humans / Male / Medical prognosis / Metastasis / Molecular Targeted Therapy / Neoplasm Metastasis / Precision Medicine / Prostate cancer / Prostatic Neoplasms - drug therapy / Prostatic Neoplasms - genetics / Prostatic Neoplasms - pathology / Prostatic Neoplasms - therapy / Quality of life / Review / Standard of Care / Testosterone / Toxicity

2025

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Therapeutic Advances in Metastatic Prostate Cancer: A Journey from Standard of Care to New Emerging Treatment

2025

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Therapeutic Advances in Metastatic Prostate Cancer: A Journey from Standard of Care to New Emerging Treatment

2025

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Journal Article

Therapeutic Advances in Metastatic Prostate Cancer: A Journey from Standard of Care to New Emerging Treatment

Litterio, Giulio,

Tătaru, Octavian Sabin,

Cicchetti, Rossella,

Ferro, Matteo,

Marchioni, Michele,

Giulioni, Carlo,

Mascitti, Marco,

Cafarelli, Angelo,

Salzano, Gaetano,

Basconi, Martina,

Digiacomo, Alessio,

Schips, Luigi,

Orsini, Angelo

2025

Overview

Prostate cancer (PCa) remains one of the most prevalent malignancies among men worldwide and continues to pose significant therapeutic challenges, especially in its metastatic and castration-resistant forms. Over the past two decades, the treatment paradigm has evolved from monotherapy with androgen deprivation therapy (ADT) to a multifaceted approach integrating chemotherapy, androgen receptor axis-targeted therapies (ARATs), radiopharmaceuticals, and precision medicine. This review explores the molecular underpinnings of PCa, including genetic and epigenetic alterations such as BRCA1/2, TP53, and PTEN mutations, and their role in disease progression and treatment resistance. We detail the evidence supporting the integration of systemic agents like abiraterone, enzalutamide, and darolutamide into both hormone-sensitive and castration-resistant settings. Furthermore, we highlight the expanding role of radioligand therapies, including radium-223 and Lutetium-177-labeled PSMA-617 (Lu-PSMA-617), as well as the growing impact of PARP inhibitors in genomically selected patients. The emergence of theranostic strategies and next-generation sequencing has paved the way for personalized treatment algorithms, moving toward a truly precision oncology model in PCa. This comprehensive review synthesizes current therapeutic strategies, clinical trial evidence, and future directions aimed at optimizing outcomes and quality of life for patients with advanced prostate cancer.

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Publisher

MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)

Subject

/ Combination therapy

/ Humans

/ Male