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用于前列腺癌治疗的PROTAC技术。

PROTAC technology for prostate cancer treatment.

作者信息

Wang Zhen, Zhang Dingpeng, Inuzuka Hiroyuki, Wei Wenyi

机构信息

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

出版信息

Acta Mater Med. 2025 Jan 7;4(1):99-121. doi: 10.15212/amm-2024-0075. Epub 2025 Jan 30.

Abstract

Prostate cancer (PrCa) is the most prevalent urogenital cancer in men, marked by uncontrolled cellular growth that leads to abnormal enlargement of the prostate gland. The metastatic spread of PrCa is the primary cause of mortality, causing cancer cells disseminate to distant sites, such as bones, the pelvis, and other organs. Key contributors to PrCa progression include genetic mutations, elevated androgen receptor (AR) expression, gene amplification, and the rise of AR splice variants. Although androgen deprivation therapy (ADT) remains the mainstay for early-stage PrCa treatment, its efficacy is rather temporary, as many cases advance to castration-resistant PrCa (CRPC), presenting a significant therapeutic hurdle. This review explores key biomarkers for PrCa and the latest therapeutic strategies for CRPC, with a particular focus on the innovative Proteolysis-targeting chimera (PROTAC) technology. This approach offers a novel means of degrading target proteins, and we discuss how PROTACs hold potential as effective strategies to combat resistance mechanisms in CRPC.

摘要

前列腺癌(PrCa)是男性中最常见的泌尿生殖系统癌症,其特征是细胞生长失控,导致前列腺异常肿大。PrCa的转移扩散是死亡的主要原因,癌细胞会扩散到远处部位,如骨骼、骨盆和其他器官。PrCa进展的关键因素包括基因突变、雄激素受体(AR)表达升高、基因扩增以及AR剪接变体的增加。尽管雄激素剥夺疗法(ADT)仍然是早期PrCa治疗的主要手段,但其疗效相当短暂,因为许多病例会发展为去势抵抗性前列腺癌(CRPC),这是一个重大的治疗障碍。本综述探讨了PrCa的关键生物标志物以及CRPC的最新治疗策略,特别关注创新的蛋白酶靶向嵌合体(PROTAC)技术。这种方法提供了一种降解靶蛋白的新手段,我们讨论了PROTAC作为对抗CRPC耐药机制的有效策略的潜力。

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