Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Curr Urol Rep. 2023 Dec;24(12):579-589. doi: 10.1007/s11934-023-01188-z. Epub 2023 Nov 21.
Despite the widespread utilization of 5-alpha reductase inhibitors (5-ARIs) for managing benign prostatic hyperplasia (BPH), certain BPH patients exhibit unresponsiveness to 5-ARIs therapy. This paper provides a comprehensive overview of the current perspectives on the mechanisms of 5-ARIs resistance in BPH patients and integrates potential biomarkers and underlying therapeutic options for 5-ARIs resistance. These findings may facilitate the development of novel or optimize more effective treatment options, and promote personalized medicine for BPH.
The pathways contributing to resistance against 5-ARIs in certain BPH patients encompass epigenetic modifications, shifts in hormone levels, autophagic processes, and variations in androgen receptor structures, and these pathways may ultimately be attributed to inflammation. Promisingly, novel biomarkers, including intravesical prostatic protrusion, inflammatory factors, and single nucleotide polymorphisms, may offer predictive insights into the responsiveness to 5-ARIs therapy, empowering physicians to fine-tune treatment strategies. Additionally, on the horizon, GV1001 and mTOR inhibitors have emerged as potential alternative therapeutic modalities for addressing BPH in the future. After extensive investigation into BPH's pathological processes and molecular landscape, it is now recognized that diverse pathophysiological mechanisms may contribute to different BPH subtypes among individuals. This insight necessitates the adoption of personalized treatment strategies, moving beyond the prevailing one-size-fits-all paradigm centered around 5-ARIs. The imperative for early identification of individuals prone to treatment resistance will drive physicians to proactively stratify risk and adapt treatment tactics in future practice. This personalized medicine approach marks a progression from the current standard treatment model, emerging as the future trajectory in BPH management.
尽管 5α-还原酶抑制剂(5-ARIs)被广泛用于治疗良性前列腺增生(BPH),但某些 BPH 患者对 5-ARIs 治疗无反应。本文全面概述了目前关于 BPH 患者 5-ARIs 耐药机制的观点,并整合了 5-ARIs 耐药的潜在生物标志物和潜在治疗选择。这些发现可能有助于开发新的或优化更有效的治疗选择,并促进 BPH 的个体化医学。
导致某些 BPH 患者对 5-ARIs 产生耐药性的途径包括表观遗传修饰、激素水平变化、自噬过程和雄激素受体结构的变化,这些途径最终可能归因于炎症。有希望的是,新的生物标志物,包括膀胱内前列腺突出、炎症因子和单核苷酸多态性,可能为 5-ARIs 治疗的反应性提供预测性见解,使医生能够调整治疗策略。此外,GV1001 和 mTOR 抑制剂有望成为未来治疗 BPH 的潜在替代治疗方法。在对 BPH 的病理过程和分子图谱进行广泛研究后,现在认识到,不同的病理生理机制可能导致个体之间存在不同的 BPH 亚型。这种认识需要采用个性化的治疗策略,超越以 5-ARIs 为中心的普遍一刀切的范式。早期识别易发生治疗抵抗的个体的必要性将促使医生在未来的实践中积极分层风险并调整治疗策略。这种个体化医学方法标志着从当前的标准治疗模式向 BPH 管理的未来轨迹的发展。