Abstract
Abstract Circulating Tumor Cells (CTCs) are present at extraordinarily low levels in the blood of patients with advanced epithelial cancers. Our group has developed and tested three generations of microfluidic devices for the isolation of CTCs, each with further improvements in automation, processing throughput and downstream analytical capabilities. Isolation and molecular analyses of these cells has a number of significant potential clinical applications: rising or declining numbers of CTCs are well correlated with tumor progression or therapeutic response. Furthermore, CTCs bear genetic hallmarks of the primary cancer, offering a noninvasive “liquid biopsy” to enable initial and serial monitoring of tumor genotypes during cancer therapy. Most significantly, CTCs hold the key to understanding the process of blood-borne metastasis. Using next generation RNA sequencing strategies, we have initiated studies of expression profiles within CTCs. These have identified cellular pathways implicated in resistance of epithelial cells to anoikis in the circulation and in epithelial-mesenchymal transition - a phenomenon implicated in cancer invasion. The heterogeneity of CTC populations is evident in single cell imaging analyses and sequencing studies, with implications for understanding the complexity of therapeutic responses. Taken together, the application of novel bioengineering technologies to the isolation and analysis of CTCs across multiple different cancer types offers a unique window into the properties of cancer cells that invade into the bloodstream and give rise to metastases. Citation Format: Daniel A. Haber, Min Yu, Emre Ozkumar, David Ting, David Miyamoto, Richard Lee, Ajay Shah, Aditya Bardia, Shannon Stott, Mehmet Toner, Shyamala Maheswaran. Molecular characterization of single circulating tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY30-01. doi:10.1158/1538-7445.AM2013-SY30-01
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