Phenotypic Heterogeneity of Circulating Tumor Cells Informs Clinical Decisions between AR Signaling Inhibitors and Taxanes in Metastatic Prostate Cancer.
Phenotypic Heterogeneity of Circulating Tumor Cells Informs Clinical Decisions between AR Signaling Inhibitors and Taxanes in Metastatic Prostate Cancer.
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DOI：
10.1158/0008-5472.can-17-1353
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发表时间：
2017-10-15
期刊：
影响因子：
11.2
通讯作者：
Dittamore R
中科院分区：
文献类型：
--
作者：
Scher HI;Graf RP;Schreiber NA;McLaughlin B;Jendrisak A;Wang Y;Lee J;Greene S;Krupa R;Lu D;Bamford P;Louw JE;Dugan L;Vargas HA;Fleisher M;Landers M;Heller G;Dittamore R
个体患者肿瘤的异质性与治疗耐药性有关，但目前缺乏在临床环境中快速、可重复地评估异质性的定量生物标志物。使用 CAP 认可和 CLIA 认证的临床实验室提供的现有工具，我们对来自 179 名独特的转移性去势抵抗性前列腺癌 (mCRPC) 患者的 9,225 个个体循环肿瘤细胞 (CTC) 的数字病理学特征进行了量化，以定义表型不同的细胞类型。使用香农指数根据个体患者样本中细胞类型的多样性对异质性进行量化，并与在开始第二线或后续线治疗之前收集的 145 个样本中的总生存期 (OS) 相关。低 CTC 表型异质性与接受雄激素受体信号抑制剂 (ARSI) 治疗的患者更好的 OS 相关，而高异质性与接受紫杉烷化疗的患者更好的 OS 相关。总体而言，结果表明量化 CTC 表型异质性有助于为 mCRPC 患者选择 ARSI 和紫杉烷类药物提供信息。
The heterogeneity of an individual patient’s tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified based on the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients.