Abstract 3196: In vivo drug sensitivity testing of CTCs isolated using the FMSA device

Abstract

Abstract BACKGROUND: Cells disseminated from primary epithelial tumors into peripheral blood, called circulating tumor cells (CTCs), can be monitored to assess metastases and to provide a surrogate marker of treatment response; indeed, the enumeration of fixed CTCs with the Johnson and Johnson Veridex CellSearch System is FDA-approved for assessment of patient prognosis in metastatic breast, prostate, and colorectal cancer. The opportunity to isolate viable CTCs using the Flexible Micro Spring Array (FMSA) device – a novel microfluidic device that enriches CTCs by two physical parameters: size and flexibility – offers the possibility of testing cancer treatments in real time and rapidly providing information back to clinicians regarding the best course of treatment. OBJECTIVES: In this study, we evaluated the possibility of isolating viable CTCs from human blood using the FMSA device, growing these cells in a mouse xenograft model, and determining successful treatments for metastatic disease. METHODS: GFP-labeled HCT-116 cells were spiked into samples of blood from healthy donors to mimic the blood of patients with metastatic disease. This spiked blood was filtered using the FMSA device, and the recovered cells were implanted into the flanks of immunodeficient mice for study. A series of in vivo experiments were carried out to investigate the effect of chemotherapy on the resulting tumors. These tumors were molecularly characterized, compared to tumors derived from non-filtered cells, and analyzed for potential differences resulting from FMSA enrichment. Studies are ongoing to further investigate the use of this model and approach to culture CTCs from patients. RESULTS & CONCLUSIONS: Cancer cells isolated from blood using the FMSA can proliferate when implanted subcutaneously into the flanks of immunodeficient mice – developing into tumors within two weeks. Although they grow at rates that depend on the number of cancer cells found in each mL of blood, these tumors provide a means for testing the effects of chemotherapy on CTCs in vivo. Using this model, treatments targeted towards CTCs could be assessed and provide real-time information to clinicians regarding treatment interventions for patients with metastatic cancer and detectable CTCs. It may also be possible to use this model as the primary mode for CTC culture as the in vivo environment may provide soluble factors, cell-to-cell interactions, and physical parameters that are not easily mimicked by in vitro culture. The approach has potential to help with efforts to develop personalized therapy options for patients with advanced cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3196. doi:1538-7445.AM2012-3196