Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called "liquid biopsy" has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.

Keywords: Circulating tumor DNA; Circulating tumor cells; Clinical application; Colorectal cancer; Exosomes; Liquid biopsy; Tumor-educated platelets.

Fig. 1

Liquid biopsy in CRC patients. CTCs, ctDNA, exosomes, CTECs, TEPs can all be detected by blood samples collected for liquid biopsy. Their analyses can be used to help with molecular profiling and treatment selection. CTCs can also be employed for culture and xenografting to help in CRC treatment selection

Fig. 2

Timeline of key discoveries of liquid biopsy

Fig. 3

Technologies for CTC and ctDNA enrichment, detection and clinical application. A CTCs are preliminary enriched from whole blood sample via different enrichment techniques. Different detection technologies can help with early detection, prognostication, chemotherapy, target therapy of CRC patients. B ctDNA are detected from whole blood sample via targeted and untargeted approaches. ctDNA can supported with early diagnosis, prognosis, disease monitoring and detected the gene mutations of CRC patients. C Exosomes are enriched from whole blood sample via different enrichment techniques. Different detection technologies can help with diagnosis, prognosis, disease monitoring, therapy of CRC patients. D TEPs are detected from whole blood sample via different approaches. TEPs can supported with early cancer detection, diagnosis, and disease monitoring of CRC patients. E CTECs are detected via different approaches. CTECs can supported with early cancer detection, diagnosis and prognosis, antiangiogenic therapy of CRC patients