Br J Cancer:转移性去势抵抗性前列腺癌中雄激素受体基因扩增状态与177Lu-PSMA-617治疗抗性相关

2021-08-01 xiaozeng MedSci原创

前列腺癌作为全球男性中第二大常见癌症,在男性癌症死亡原因中排名第六。

前列腺癌作为全球男性中第二大常见癌症,在男性癌症死亡原因中排名第六。晚期疾病患者的标准护理主要基于雄激素剥夺疗法(ADT),然而,尽管睾酮处于去势水平,该疾病仍可能会发展为去势抵抗性前列腺癌(CRPC)。

既往研究显示,雄激素受体(AR)的畸变与去势抵抗的主要机制相关,去势抵抗是转移性去势抵抗性前列腺癌(mCRPC)患者死亡的主要原因。


前列腺特异性膜抗原(PSMA)是一种锚定在前列腺上皮细胞膜上的蛋白酶,是mCRPC诊断和治疗的一个潜在的有前景的靶标。研究人员发现,前列腺癌的较高级别评分与PSMA的表达水平升高相关。

近期,一种名为177Lu-PSMA-617的治疗诊断剂被用于mCRPC患者的临床治疗,177Lu-PSMA-617是一种177Lutethium(177Lu)标记的PSMA抑制剂。


在该2期临床试验中,研究人员旨在确定177Lu-PSMA-617的活性以及在经过标准延长生命治疗后疾病出现进展的重度预处理mCRPC患者中的最小有效剂量,并确定血浆AR状态能否预测患者的早期反应或疾病进展。

血浆AR状态与PSA响应的关系

研究人员通过分析预处理血浆样品中AR的拷贝数。采用逻辑回归评估AR状态的独立相关性,并鉴定早期进展性疾病(PD)患者,指在177Lu-PSMA-617治疗后的四个月内出现治疗中断。


结果显示,15名具有AR基因增益的患者和25名无AR增益的患者中分别有12名(80%)和5名(20%)患有早期PD。无PSA响应且AR增益的患者的OR(风险比)为3.69。具有AR增益的早期PD患者的OR为16.00。

AR状态与患者临床结局的关系

总体而言,患者的中位PFS(无进展生存期)和OS(总体生存期)分别为7.5和12.4个月。相比于AR正常的患者,AR增益患者的OS显着缩短(7.4个月 vs 19.1个月)。并无报告因不良反应而出现的治疗中断。


总而言之,该研究结果揭示,血浆AR状态有助于分析mCRPC患者对177Lu-PSMA-617治疗的早期抗性。


原始出处:

De Giorgi, U., Sansovini, M., Severi, S. et al. Circulating androgen receptor gene amplification and resistance to 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: results of a Phase 2 trial. Br J Cancer (31 July 2021).

 

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    2021-08-03 江川靖瑶
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    2021-08-02 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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