Complex interactions with blood constituents combined with the expression of specific genetic signatures, which seem to be associated with the ability of CTCs to metastasize (e.g., in a study by Zhang et al.[41], breast cancer CTCs expressing the Her2+/EGFR+/HPSE+/Notch1+ genetic signature demonstrated a tendency to metastasize in the brain), allow an extremely small fraction of cancer cells in the bloodstream to complete the metastatic cascade, thus colonizing distant tissues and promoting the generation of new tumor lesions. The gene discussed is NOTCH1; the disease is breast carcinoma.