Danielli Linda, Tassinari Elisa, Marchetti Andrea, Rosellini Matteo, Mollica Veronica, Cheng Liang, Massari Francesco
Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Expert Rev Anticancer Ther. 2025 May;25(5):457-470. doi: 10.1080/14737140.2025.2481141. Epub 2025 Mar 20.
Prostate cancer represents a significant oncological challenge, with its natural history predominantly driven by androgen receptor (AR) signaling. The pivotal role of this pathway underscores the rationale for targeting AR activity in therapeutic strategies. However, the development of resistance mechanisms has highlighted the need for advanced therapies to address the complexity of the castration-resistant status.
We analyzed the evolving role of second-generation androgen receptor signaling inhibitors (ARSIs) in the management of non-metastatic and metastatic castration-resistant prostate cancer, we critically examine emerging combination strategies involving ARSIs, novel agents targeting resistance pathways, and the mechanisms underlying treatment resistance. The review also provides insights into future directions for enhancing outcomes. PubMed literature research using keywords related to castration-resistant prostate cancer and its treatments was performed, including the most relevant trials and reviews.
ARSIs have revolutionized the management of prostate cancer, providing substantial clinical benefits and representing the cornerstone of current treatment paradigms. However, key challenges remain, including determining optimal treatment sequencing, overcoming resistance mechanisms, and tailoring therapies to specific molecular subtypes. Biomarker-driven approaches are critical for refining patient selection and improving therapeutic outcomes. Ongoing trials investigating novel hormonal-axis-directed agents and innovative combination therapies aim to expand the arsenal of effective treatment.
前列腺癌是一项重大的肿瘤学挑战，其自然病程主要由雄激素受体（AR）信号传导驱动。该信号通路的关键作用凸显了在治疗策略中靶向AR活性的基本原理。然而，耐药机制的出现突出了需要先进疗法来应对去势抵抗状态的复杂性。
我们分析了第二代雄激素受体信号抑制剂（ARSIs）在非转移性和转移性去势抵抗性前列腺癌管理中的不断演变的作用，我们批判性地审视了涉及ARSIs的新兴联合策略、针对耐药途径的新型药物以及治疗耐药的潜在机制。该综述还提供了关于改善治疗结果的未来方向的见解。使用与去势抵抗性前列腺癌及其治疗相关的关键词进行了PubMed文献研究，包括最相关的试验和综述。
ARSIs彻底改变了前列腺癌的管理，带来了显著的临床益处，是当前治疗模式的基石。然而，关键挑战仍然存在，包括确定最佳治疗顺序、克服耐药机制以及针对特定分子亚型量身定制治疗方案。生物标志物驱动的方法对于优化患者选择和改善治疗结果至关重要。正在进行的研究新型激素轴导向药物和创新联合疗法的试验旨在扩大有效治疗的武器库。
