Abstract IA29: Circulating Tumor Cells: A liquid biopsy for SCLC with multiple applications

Abstract

Abstract Circulating Tumor Cells (CTCs) are relatively prevalent in SCLC compared to other tumor types and present several research opportunities in a disease where tumor biopsy is challenging, and notably so when repeated sampling is required. Pre-treatment CTC number by the CellSearch platform (CS-CTCs) is prognostic for overall survival and in most patients decreases significantly after cycle 1 of platinum-based chemotherapy. The prevalence and wide dynamic range of CS-CTC numbers makes them an ideal pharmacodynamic biomarker, and their prevalence affords assay development and implementation as a predictive biomarker in upcoming trials of novel treatments. Recently we showed that chemotherapy response could be predicted via single CTC sequencing to generate a CTC copy number signature (Carter et al., Nat Med 2017). SCLC patients’ CTCs are also highly tumorigenic in immune-compromised mice (Hodgkinson et al., Nat Med 2014). CDX mirror patient tumor histology and chemotherapy response. The resultant CTC-derived explant models (CDX) can be generated not only at baseline but also from the same patient at disease progression, allowing studies of the almost universal acquired chemotherapy resistance and insights into the rapid evolution of this dismal disease. CDX are used for therapy testing and biomarker development that can be translated to CTC-based biomarkers in the clinic. CDX allow exploration of SCLC biology as we recently exemplified by the identification of vasculogenic mimicry and its likely role in metastasis (Williamson et al., Nat Commun 2016). CDX tumors can be disaggregated and propagated in culture for more rapid treatment screening and can be genetically manipulated for function testing hypotheses ex vivo and in vivo. Finally, SCLC CTCs can now be cultured directly from the patient sample, offering the potential for real-time treatment testing. In summary, SCLC CTC research can now make a valuable contribution to the worldwide efforts to molecularly profile this recalcitrant tumor at all stages of disease progression and to discover, develop, and implement new treatments for much-needed improved patient outcomes. Citation Format: Caroline Dive. Circulating Tumor Cells: A liquid biopsy for SCLC with multiple applications [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA29.