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在PSMA向治疗之前,对化疗前的前列腺癌进行基因组分析

Mariam Amghar¹, Mareike Roscher², Tobias Rausch³

¹Junior Research Group Translational Radiotheranostics, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Frontiers in oncology

|February 20, 2026

概括

接受双重PSMA-RPT的化学疗法原始转移性割抵抗性前列腺癌 (mCRPC) 患者表现出特定的基因组变化. 基线循环瘤DNA (ctDNA) 分析显示,在这些罕见的情况下,经常出现染色体失衡,如8p损失和8q增益.

科学领域:

在瘤学瘤学.
基因组学就是基因组学.
放射性药物疗法是一种放射性药物疗法.

背景情况:

转移性割抵抗性前列腺癌 (mCRPC) 治疗通常包括化学疗法,然后再进行双重放射性核酸治疗.
接受双重 [225Ac]Ac-/[177Lu]Lu-PSMA-617 治疗的化学疗法原始患者很少见,反应/耐药性的基因组基础尚不清楚.
前列腺特异性膜抗原放射性药物治疗 (PSMA-RPT) 结果的基线基因组预测因子尚未确定.

研究的目的:

探索罕见的化学疗法以前的mCRPC患者的分子特征,这些患者接受了双重PSMA-RPT治疗.
在这个独特的患者队列中调查治疗结果的基线基因组预测因素.
在PSMA-RPT开始时,分析循环瘤DNA (ctDNA) 的拷贝数变化 (CNAs).

主要方法:

从接受 [225Ac]Ac-/[177Lu]Lu-PSMA-617治疗的mCRPC患者收集的血液样本.
隔离了无细胞DNA (cfDNA) 并进行了超低通量全基因组测序 (ULP-WGS).
使用 ichorCNA 算法推断全基因组 CNA 和瘤分数 (TFx).

主要成果:

分析了五名化学疗法未经治疗的患者的cfDNA (四个基线,一个纵向).
确定了包括1q,7q和8q染色体的放大和8p中的损失在内的复发性CNAs.
尽管临床进展,但在一名患者中观察到稳定的8p损失和8q增益,这表明持续的基因组驱动因素.

结论:

在未接受化疗的mCRPC患者中,基线cfDNA CNA 分析揭示了反复出现的染色体失衡.
在这种情况下,8p的损失和8q的增加可能代表了晚期前列腺癌的内在,稳定的特征.
基于cfDNA的基因组学显示出探索罕见PSMA-RPT队列的潜力.

关键词:

在PSMA上,PSMA可以在PSMA上进行交易.cfDNA DNA 的时间.化学疗法-先前没有接受过化疗.副本编号的交替副本编号的交替 mCRPC 的使用情况.放射性药物疗法是一种放射性药物疗法.两者同时进行的动-治疗.

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