Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells

被引：105

作者：

Wang, Lihua ^{[1
]}

Balasubramanian, Priya ^{[1
]}

Chen, Alice P. ^{[2
]}

Kummar, Shivaani ^{[2
]}

Evrard, Yvonne A. ^{[1
]}

Kinders, Robert J. ^{[1
]}

机构：

[1] Leidos Biomed Res Inc, Appl Dev Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA

[2] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA

来源：

SEMINARS IN ONCOLOGY | 2016年 / 43卷 / 04期

基金：

美国国家卫生研究院;

关键词：

CTCs; Assay validation; Surrogate endpoint; Pharmacodynamics; RESISTANT PROSTATE-CANCER; METASTATIC BREAST-CANCER; PROGRESSION-FREE SURVIVAL; PREDICTIVE BIOMARKER; ABIRATERONE ACETATE; OVARIAN-CANCER; LUNG-CANCER; PHASE-I; VELIPARIB; BLOOD;

D O I：

10.1053/j.seminoncol.2016.06.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Circulating tumor cells (CTCs), which are captured from blood with anti-epithelial cell adhesion molecule (EpCAM) antibodies, have established prognostic value in specific epithelial cancers, but less is known about their utility for assessing patient response to molecularly targeted agents via measurement of pharmacodynamic (PD) endpoints. We discuss the use of CellSearch (Janssen Diagnostics, LLC, Raritan, NJ) CTC isolation technology for monitoring PD response in early phase trials. We present representative data from three clinical trials with the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) suggesting that CTCs can be used to measure PD effects. However, while often leading to hypothesis generating information, our experience points to the difficulty in obtaining sufficient EpCAM-expressing CTCs from patients with advanced disease to reach statistically significant conclusions about PD effects from each trial. Overall, the level of phenotypic heterogeneity observed in specimens from patients with advanced carcinomas suggests caution in the use of cell-surface differentiation marker-based methods for isolating CTCs. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：464 / 475

页数：12

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