Liquid biopsy: one cell at a time

As an alternative target to surgically resected tissue specimens, liquid biopsy has gained much attention over the past decade. Of the various circulating biomarkers, circulating tumor cells (CTCs) have particularly opened new windows into the metastatic cascade, with their functional, biochemical, and biophysical properties. Given the extreme rarity of intact CTCs and the associated technical challenges, however, analyses have been limited to bulk-cell strategies, missing out on clinically significant sources of information from cellular heterogeneity. With recent technological developments, it is now possible to probe genetic material of CTCs at the single-cell resolution to study spatial and temporal dynamics in circulation. Here, we discuss recent transcriptomic profiling efforts that enabled single-cell characterization of patient-derived CTCs spanning diverse cancer types. We further highlight how expression data of these putative biomarkers have advanced our understanding of metastatic spectrum and provided a basis for the development of CTC-based liquid biopsies to track, monitor, and predict the efficacy of therapy and any emergent resistance.