The development and applications of circulating tumour cells, circulating tumour DNA and other emerging biomarkers for early cancer detection.

Despite major improvements in cancer treatment, detection, and health promotion, the mortality rates of late-stage cancer remain high. This is a critical issue because a large proportion of cancer mortality is experienced by patients who have late-stage disease at diagnosis. As survival is substantially higher for almost all cancers when diagnosed at an early stage, effective early cancer detection strategies could drastically reduce overall cancer mortality. Advances in various technologies have culminated in the development of liquid biopsies. The tumour biomarkers applied for non- or minimally-invasive cancer detection include tumour cells and their components in bodily fluids, especially peripheral blood for circulating tumour biomarkers. The most well-studied circulating tumour biomarkers in recent years for the early detection of cancer are circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), with research into other classes rapidly expanding. CTCs and ctDNA have been detected at an early stage in several types of cancer with high specificity, aiding risk stratification and, in some cases, identifying clinically actionable molecular features. Therefore, these circulating biomarkers offer several advantages over the traditional cancer detection methods. Although their limitations are considerable, the evolving evidence suggests they have tremendous potential as tools for early cancer detection. In this review, we evaluate the development and applications of circulating biomarkers for early cancer detection, with a focus on CTCs and ctDNA. We also briefly explore the emerging evidence on extracellular vesicles, circulating proteins and synthetic biomarkers, discuss the limitations of current approaches and provide suggestions to achieve further progress in this setting.