Abstract：
OBJECTIVE: 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.
RESULTS: 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.
RESULTS: 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.
摘要：
目的：尽管广泛使用5-α还原酶抑制剂（5-ARIs）治疗良性前列腺增生（BPH），某些BPH患者对5-ARIs治疗无反应。本文对BPH患者5-ARIs耐药机制的当前观点进行了全面概述，并整合了潜在的生物标志物和5-ARIs耐药的潜在治疗选择。这些发现可能有助于开发新的或优化更有效的治疗方案，并促进BPH的个性化医疗。
结果：某些BPH患者对5-ARIs耐药的途径包括表观遗传修饰，激素水平的变化，自噬过程，以及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,新型生物标志物，包括膀胱内前列腺突出，炎症因子，和单核苷酸多态性，可以提供对5-ARIs治疗反应性的预测性见解，授权医生微调治疗策略。此外,在地平线上,GV1001和mTOR抑制剂已成为未来解决BPH的潜在替代治疗方式。经过对BPH的病理过程和分子景观的广泛调查，现在已经认识到，不同的病理生理机制可能导致个体之间不同的BPH亚型。这种洞察力需要采用个性化的治疗策略，超越了以5-ARI为中心的普遍的一刀切的范式。早期识别容易产生治疗抵抗的个体的必要性将促使医生在未来的实践中主动分层风险并调整治疗策略。这种个性化的医疗方法标志着从目前的标准治疗模式的进步，正在成为BPH管理的未来轨迹。
结果：某些BPH患者对5-ARIs耐药的途径包括表观遗传修饰，激素水平的变化，自噬过程，以及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,新型生物标志物，包括膀胱内前列腺突出，炎症因子，和单核苷酸多态性，可以提供对5-ARIs治疗反应性的预测性见解，授权医生微调治疗策略。此外,在地平线上,GV1001和mTOR抑制剂已成为未来解决BPH的潜在替代治疗方式。经过对BPH的病理过程和分子景观的广泛调查，现在已经认识到，不同的病理生理机制可能导致个体之间不同的BPH亚型。这种洞察力需要采用个性化的治疗策略，超越了以5-ARI为中心的普遍的一刀切的范式。早期识别容易产生治疗抵抗的个体的必要性将促使医生在未来的实践中主动分层风险并调整治疗策略。这种个性化的医疗方法标志着从目前的标准治疗模式的进步，正在成为BPH管理的未来轨迹。
