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同时发生的BRCA2 / SPOP突变预测异常多 (ADP-ribose) 聚合酶抑制剂在转移性化抵抗性前列腺癌中的敏感性

Jacob J Orme¹, Fadi Taza², Navonil De Sarkar³

¹Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.

European urology oncology

|December 10, 2023

概括

接受多 (ADP-ribose) 聚合酶 (PARP) 抑制剂的BRCA2和SPOP突变患者在转移性割抵抗性前列腺癌中表现出改善的结果. 这表明SPOP突变可能会增强BRCA2-改变的mCRPC中PARP抑制剂的有效性.

科学领域:

在瘤学瘤学.
遗传学是一个遗传学.
癌症研究癌症研究

背景情况:

具有BRCA2突变的转移性割抵抗性前列腺癌 (mCRPC) 对PARP抑制剂有反应.
需要额外的生物标志物来预测mCRPC中PARP抑制剂的疗效.
临床前数据表明,SPOP无活化可能会增强PARP抑制剂的敏感性.

研究的目的:

调查SPOP突变是否预测BRCA2-改变的mCRPC中增强的PARP抑制剂反应.
为了比较BRCA2突变患者与并发SPOP突变或没有并发SPOP突变患者的临床结果,用PARP抑制剂治疗.

主要方法:

一个多中心的回顾性研究,对131名BRCA2改变的mCRPC患者进行了PARP抑制剂治疗.
在BRCA2mut/SPOPwt (n=14) 和BRCA2mut/SPOPwt (n=117) 疾病的患者之间比较结果 (PSA反应,PFS,OS).
使用多变量Cox比例危险模型,调整临床和基因组因素.

主要成果:

患有BRCA2突变/SPOP突变疾病的患者表现出更高的PSA应答率 (86%vs60%) 和更长的中位治疗持续时间 (24.0vs8.0个月).
多变量分析显示,BRCA2mut/SPOPmut患者的PSA-PFS (调整HR 0.16),临床/放射性PFS (调整HR 0.28) 和OS (调整HR 0.19) 显著更长.
基因组分析表明BRCA2突变/SPOP突变疾病中HRR缺陷得分较高.

结论:

与BRCA2和SPOP的共同改变预测与单独的BRCA2改变相比,在mCRPC中PARP抑制剂治疗的优异结果.
增强的疗效可能与两种突变患者同源复合修复 (HRR) 缺陷的增加有关.
进一步的前性验证是合理的.

关键词:

这是一种BRCA2突变.聚 ((ADP-ribose) 聚合酶抑制剂的多种类型在SPOP突变的过程中,SPOP突变.

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