Beyond epithelial circulating tumour cells (CTCs) : establishing important methods for CTC isolation and analysis

Abstract

This thesis has demonstrated the various applications for antibody-based CTC capture, extending beyond conventional methods. We reported the inclusion of EMT-markers for detection and characterisation of EMT-CTCs in the ovarian cancer setting. This methodological advancement may prove a critical step in understanding the role EMT plays in CTC formation, metastasis and potentially therapeutic resistance. In addition, we explored integration of electron microscopy methods into CTC sample processing, allowing for ultrastructure analysis of CTCs and improving the tools to help understand CTC biology. Finally, we explored antibody-based CTC isolation methods in the melanoma setting with additional biomarker PD-L1 detection, enabling real-time monitoring of therapy response to PD-1 inhibitors. Overall, the knowledge gained from this thesis will aid the CTC research field from three different perspectives: (1) The clinical perspective: capitalize on CTC detection by adding important biomarker detection that may indicate response to therapy; (2) The technical perspective: demonstrating feasibility of integrating electron microscopy sample preparation into CTC analyses; (3) The biological perspective: establishing EMT detection in a range of cancers

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