Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells |
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| Institution: | 1. Division of Hematology & Medical Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, United States;2. Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, United States;1. Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin University, Harbin, China;3. Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China |
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| 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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| Keywords: | CTCs Assay validation Surrogate endpoint Pharmacodynamics |
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