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 journalReview articlepeer-review

39 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 languageEnglish (US)
Pages (from-to)464-475
Number of pages12
JournalSeminars in Oncology
Volume43
Issue number4
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Keywords

  • Assay validation
  • CTCs
  • Pharmacodynamics
  • Surrogate endpoint

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells'. Together they form a unique fingerprint.

Cite this