Abstract A031: Harnessing the potential of circulating tumour cells for precision diagnostics via multiplexed imaging of the levels and subcellular localizations of over 50 cell identity, state and signaling markers per cell

作者：John G. Lock, Tim J Mann, Zheng Ye, Tanzila Khan, Daniel Neumann, Alexander C. James, Therese M. Becker, Tara L. Roberts · 发表于：Clinical Cancer Research · 年份：2024 · DOI：10.1158/1557-3265.liqbiop24-a031 · 被引用次数：2 · 研究领域：3D Printing in Biomedical Research、Cancer Cells and Metastasis

Abstract Due to their longitudinal accessibility through liquid biopsy, circulating tumour cells (CTCs) hold huge potential as sources of molecular information capable of underpinning precision diagnostics in cancer. Yet key methodological limitations have thus far constrained the practical utility of CTCs as diagnostic analytes, including: a) reliance on positive CTC selection strategies that can bias against distinctive CTC subpopulations (e.g. low EpCAM, low size, low density), and; b) standard fluorescence imaging methods that capture only 4-6 molecular markers per cell. Since 3-4 markers are required to identify CTCs with even moderate confidence, such low marker plexity acutely restricts derivation of additional molecular insights about the cellular states and molecular signals that may be driving disease. Yet these insights are essential to guide selection of optimal therapies, to adapt therapeutic strategies as cycles of resistance arise, and even to stratify patients to the trials needed to expand the therapeutic arsenal. To overcome these challenges and harness the potential of CTCs for precision diagnostics, we have developed a comprehensive pipeline for CTC isolation, storage and batch processing via multiplexed immunofluorescence imaging of 50+ molecular markers per cell. These markers illuminate CTC identity, state (epithelial vs mesenchymal vs stemness), fate (proliferation, death, senescence) and signalling (spanning ∼10 alternate ‘driver’ signalling pathways)...