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CLIN CANCER RES：Alisertib治疗神经内分泌前列腺癌

2019-01-20 MedSci MedSci原创

神经内分泌前列腺癌Alisertib去势抵抗
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神经内分泌前列腺癌（NEPC）是一种侵袭性前列腺癌，可能是治疗耐药的机制。N-myc能够促进NEPC进展。Alisertib能够抑制N-myc与Aurora-A之间的相互作用，抑制N-myc信号传导，抑制肿瘤生长。CLIN CANCER RES近期发表了一篇文章，报道了Alisertib治疗NEPC的研究结果。

神经内分泌前列腺癌（NEPC）是一种侵袭性前列腺癌，可能是治疗耐药的机制。N-myc能够促进NEPC进展。Alisertib能够抑制N-myc与Aurora-A之间的相互作用，抑制N-myc信号传导，抑制肿瘤生长。CLIN CANCER RES近期发表了一篇文章，报道了Alisertib治疗NEPC的研究结果。

60名男性接受每周两次Alisertib 50mg治疗，21天一个周期。入组标准包括转移性前列腺癌以及至少一种以下情况：小细胞神经内分泌形态； ≥50％神经内分泌标志物表达； 没有PSA进展的新发肝转移； 或血清神经内分泌标志物升高。主要终点是6个月影像学无进展生存期（rPFS）。通过全外显子组测序和RNA-seq研究治疗前肿瘤标本。研究结果表明：中位PSA为1.13 ng / mL，既往治疗次数为3次，内脏转移率为68％。基因组改变涉及RB1（55％），TP53（46％），PTEN（29％），BRCA2（29％）和AR（27％），并且存在一系列雄激素受体信号传导和NEPC标志物表达。6个月的rPFS为13.4％，中位总生存期为9.5个月。观察到治疗反应，包括肝转移的完全消退和疾病长期稳定，肿瘤显示出N-myc和Aurora-A过度活动。

文章最后认为，虽然该研究未达到其主要终点，但是一部分具有Aurora-A和N-myc活化分子特征的晚期前列腺癌患者可以从单药alisertib治疗明显获益。

原始出处：

Himisha Beltran, Clara Oromendia, et al. A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers. CLIN CANCER RES. January 2019 doi: 10.1158/1078-0432.CCR-18-1912

本文系梅斯医学（MedSci）原创编译整理，转载需授权！


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    2019-09-05 lily1616

    #神经内分泌#

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    2019-12-31 ms1343860338762272

    #Alisertib#

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    2019-08-11 gwc392

    #分泌#

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