靶向DHCR7协同恩杂鲁胺诱导线粒体凋亡并重塑免疫抑制性肿瘤微环境抑制CRPC

By targeting the DHCR7 axis and combining calcitriol with enzalutamide, the problem of enzalutamide resistance in castration-resistant prostate cancer was solved, achieving tumor cell apoptosis and immune remodeling, reducing economic burden and medical costs, and prolonging patient survival.

CN121177312BActive Publication Date: 2026-07-17THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
THE FIFTH AFFILIATED HOSPITAL SUN YAT SEN UNIV
Filing Date
2025-08-29
Publication Date
2026-07-17

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Abstract

本发明属于癌症治疗技术领域，公开了靶向DHCR7协同恩杂鲁胺诱导线粒体凋亡并重塑免疫抑制性肿瘤微环境抑制CRPC。本发明发现耐药细胞表现出显著的胆固醇积累和胆固醇酯降低，同时伴有7‑DHC的耗竭，药物治疗能够恢复7‑DHC的水平，引发依赖于活性氧(ROS)的线粒体损伤，并使肿瘤对恩杂鲁胺重新敏感。骨化三醇与恩杂鲁胺协同作用，克服耐药性并激活抗肿瘤免疫，将数十年来关于维生素D缺乏与侵袭性前列腺癌之间的关联的流行病学观察结果与可行的治疗策略联系起来。这些结果不仅拓展了我们对去势抵抗性前列腺癌(CRPC)中代谢异质性的理解，还为利用现有疗法来对抗致命的治疗耐药性提供了一个基于生物标志物的框架。
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