Abstract

Abstract The IMI-funded CANCER-ID consortium (https://www.cancer-id.eu/) was created in order to facilitate the use of Circulating Tumor Cells (CTCs) and other liquid biopsies (ctDNA, miRNA, exosomes) in the monitoring and treatment of cancer, via establishing and validating protocols for their detection and characterization. CTCs are tumor cells that have passively or actively migrated from the bulk of the primary or metastatic tumor(s) into the peripheral blood stream. While some of these cells may establish new metastases and mediate outgrowth of the disease, they can also serve as diagnostic, prognostic or potentially predictive biomarkers, providing non-invasive access to tumor material and information on tumor evolution. However, a major challenge remains in the identification of these very rare cells (1:106-8 WBCs). In the past years, a plethora of methods have been developed to isolate CTCs, via antibody enrichment/depletion strategies, size exclusion and/or based on density and dielectric properties. Yet despite this progress, the detection rate of CTCs in NSCLC (non-small cell lung cancer) is still very low (only ca. 20-30% of metastatic NSCLC patients have detectable CTCs). In stark contrast, SCLC (small cell lung cancer) patients have usually hundreds of detectable CTCs. A potential reason for the lack of detection of NSCLC CTCs may be the choice of surface markers used to detect the CTCs. Using NSCLC cell lines spiked into healthy donor blood, novel antibody cocktails, including positive and negative selection markers, and also markers for cells undergoing epithelial-mesenchymal transition were tested for their sensitivity and specificity to detect tumor cells in blood. Blood samples from NSCLC and SCLC patients are currently being analyzed using the Cell Search system (an EpCAM-based, FDA approved device - the current ‘gold standard' for CTC detection and enumeration), in parallel with the Parsortix device (a micro-fluidic platform that isolates CTCs according to size and deformability). This direct comparison permits an understanding of whether the combination of the Parsortix device with downstream novel antibody cocktails for CTC identification improves sensitivity, over Cell Search, while still retaining good selectivity. Results from this ongoing study will be presented. The goal of this project is to generate and clinically validate a protocol that would enable the use of CTCs as a liquid biopsy for NSCLC patients. Such an approach would be of particular benefit to these patients, since tumor biopsies cannot always being readily attained and the use of invasive intervention carries some risk of bleeding and infection. This work is supported by IMI JU & EFPIA (grand no. 115749). Citation Format: Linda Scarrott, Hanny Musa, Harriet Wikman, Sonja Loges, Juergen Braunger, Klaus Pantel, Ralph Graeser. CANCER ID and the identification of circulating tumor cells (CTCs) in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3610.

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