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

Lihua Wang; Priya Balasubramanian; Alice P. Chen; Shivaani Kummar; Yvonne A. Evrard; Robert J. Kinders

doi:10.1053/j.seminoncol.2016.06.004

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

Lihua Wang, Priya Balasubramanian, Alice P. Chen, Shivaani Kummar, Yvonne A. Evrard, Robert J. Kinders

Research output: Contribution to journal › Review article › peer-review

92 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	464-475
Number of pages	12
Journal	Seminars in Oncology
Volume	43
Issue number	4
DOIs	https://doi.org/10.1053/j.seminoncol.2016.06.004
State	Published - Aug 1 2016
Externally published	Yes

Keywords

Assay validation
CTCs
Pharmacodynamics
Surrogate endpoint

ASJC Scopus subject areas

Hematology
Oncology

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10.1053/j.seminoncol.2016.06.004

Cite this

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title = "Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells",

abstract = "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.",

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AU - Wang, Lihua

AU - Balasubramanian, Priya

AU - Chen, Alice P.

AU - Kummar, Shivaani

AU - Evrard, Yvonne A.

AU - Kinders, Robert J.

PY - 2016/8/1

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N2 - 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.

AB - 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.

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KW - Surrogate endpoint

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

Abstract

Keywords

ASJC Scopus subject areas

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