Abstract
We have previously developed a fluid phase biopsy technology that reliably identifies rare circulating tumor cells (CTCs) found in the peripheral blood of cancer patients. This enrichment-free high-definition single-cell assay (HD-SCA) technology combines immunofluorescent staining and automated digital microscopy to target individual CTCs and circulating tumor microemboli (CTC clusters), generating high-quality and high-resolution digital images for detailed characterization of cellular morphology and protein expression. Recent developments have pushed the assay to the point of genome-wide copy number variation in single cells and multiplexed protein imaging with subcellular precision. Connecting the dynamics across this range of scales yields a comprehensive profile of the state of the disease at sequential time points during treatment. Here we describe the application of the HD-SCA to investigate tumor cells in the blood and bone marrow aspirates of metastatic castrate-resistant prostate cancer (mCRPC) patients. We observe a broad spectrum of tumor cell subpopulations that differ in morphometric parameters, such as cell size and shape, and relative expression levels of cytokeratin and androgen receptor—the latter a key driver in the progression of prostate cancer and target of several current therapies. Additional genomic profiling, subcellular protein expression measurements, and clinical correlates over space and time are currently underway to study CTC origins, travel strategies, and implications on disease progression. Taken together, this type of multidimensional assessment will enable our ability to measure relevant changes in cancer behavior that, when integrated into the current standard of care, will likely result in improved clinical outcomes.
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