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在转移性割抵抗性前列腺癌患者中,AR变化告知了循环瘤DNA检测

Todd P Knutson¹, Bin Luo², Anna Kobilka³

¹Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA.

Nature communications

|December 11, 2024

概括

使用AR-ctDETECT检测方法检测前列腺癌患者的循环瘤DNA (ctDNA) 表明,即使使用先进的治疗方法,幸存率也很差. 这一发现突出了ctDNA的发现.

科学领域:

在瘤学瘤学.
遗传学是一个遗传学.
分子生物学分子生物学

背景情况:

流通瘤DNA (ctDNA) 在血细胞自由DNA (cfDNA) 中是癌症的预后标志物.
由于血体积有限,检测ctDNA具有挑战性,特别是在转移性割抵抗性前列腺癌 (mCRPC) 中.
准确的ctDNA测定对于预测使用雄激素受体 (AR) 抑制剂治疗mCRPC患者的结果至关重要.

研究的目的:

开发和验证一种定制的向cfDNA测序试验AR-ctDETECT,用于检测mCRPC患者的ctDNA.
评估使用AR-ctDETECT在mCRPC患者中的ctDNA检测的预后价值,来自第三期临床试验.

主要方法:

开发针对性cfDNA测序的AR-ctDETECT试验.
在联盟A031201试验中,对mCRPC患者的血样本进行测定.
对ctDNA阳性的分析,包括形,AR变化,MYC/MYCN增益和突变,与患者存活率相关.

主要成果:

在776名mCRPC患者中,59%的AR-ctDETECT测定检测到ctDNA.
与ctDNA阴性患者 (47.4个月) 相比,ctDNA阳性患者的平均整体存活期 (29.0个月) 显着较差.
具体的ctDNA变化包括高ctDNA无倍化 (26%),低ctDNA无倍化与AR增益/重组 (33%),MYC/MYCN增益或致病突变.

结论:

该AR-ctDETECT测定有效地识别了mCRPC患者的ctDNA与有限的血cfDNA.
根据AR-ctDETECT的测定,ctDNA阳性是mCRPC患者生存率低下的强有力的预测指标,无论强大的AR抑制剂治疗如何.
这种测试为mCRPC患者提供了宝贵的预后信息,这些患者在3期临床试验环境中接受治疗.

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