Abstract
BACKGROUND: Circulating tumour cells (CTCs) are cancer cells that circulate in the bloodstream after being shed from solid tumours. They can lead to tumour recurrence and metastasis. CTCs play a significant role as biomarkers for early diagnosis, therapy response monitoring, and prognostication. However, CTCs are rare and heterogeneous, with usually only a single-digit number in one millilitre of blood. Additionally, a circadian rhythm is involved in the release of CTCs into the peripheral circulation. Due to these biological properties, higher demands are placed on the isolation of CTCs, and current capture methods struggle to enrich all CTCs present in blood. As yet, these limitations have hampered the clinical application of CTCs. CONCLUSIONS: In this review, we focus on the biological properties and clinical applications of CTCs and current CTC enrichment and isolation methods. Combined enrichment methods based on physical and biological properties are considered instrumental for the development of highly specific and sensitive CTC capture methods. The utilization of CTCs in conjunction with other liquid biopsy components (such as ctDNA) may yield more clinically useful information and the circadian rhythmicity of CTC release may change the way to evaluate and treat patients.