清脆的
恩扎鲁胺
前列腺癌
生物
PAK1号
抗药性
遗传学
基因
癌症
癌症研究
生物信息学
内科学
医学
肿瘤科
信号转导
雄激素受体
作者
Haojie Chen,Keqin Dong,Jie Ding,Jia Xia,Fajun Qu,Lan-Yun Feng,Haihong Liao,Yuhang Qian,Jiacheng Huang,Zihan Xu,Zhengqin Gu,Bowen Shi,Mingming Yu,Xingang Cui,Haojie Chen
出处
期刊:Cancer Letters
[Elsevier]
日期:2024-04-01
卷期号:587: 216725-216725
被引量:4
标识
DOI:10.1016/j.canlet.2024.216725
摘要
Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. PAK1 drives ARSI cross-resistance in prostate cancer progression.
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