Abstract PL06-04: Molecular characterization of circulating tumor cells.

Abstract

Abstract Circulating tumor cells (CTCs) are present at extraordinarily low levels in the blood of patients with non-hematological cancers, but they provide a non-invasive source of cancer cells for potential diagnostic applications, as well as for understanding the process of blood-borne metastasis. We have 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. The CTC-iChip allows high throughput and high efficiency depletion of normal leukocytes through a microfluidic magnetophoresis device, revealing untagged CTCs. The unbiased isolation of CTCs irrespective of tumor epitopes, together with their presentation in a format where they can be readily manipulated, provides unique opportunities for their detailed molecular characterization. We have previously shown that rising or declining numbers of CTCs are well correlated with tumor progression or therapeutic response; that they can be used to monitor the prevalence of known clinically-relevant mutations; and that changes in their composition can be followed longitudinally during the course of targeted cancer therapies. Epithelial-to-mesenchymal transition (EMT) is evident among CTCs and evolves dynamically during the course of response or progression following cancer therapy. The heterogeneity of CTC populations is evident in single cell imaging analyses and sequencing studies, with implications for understanding the complexity of metastatic progression and 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 Information: Mol Cancer Ther 2013;12(11 Suppl):PL06-04. Citation Format: Daniel A. Haber, Shyamala Maheswaran, Lecia Sequist, Min Yu, Emre Ozkumur, David Ting, David Miyamoto, Richard Lee, Ajay Shah, Aditya Bardia, Shannon Stott, Mehmet Toner. Molecular characterization of circulating tumor cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr PL06-04.