“…Despite the discovery of numerous CTC-specific CSMs, the main limitation that hampers existing CTC detection technologies is still the a priori knowledge of the exact protein composition on the CTCs surfaces, and the lack of a universal marker(s) to address the heterogeneity of CTCs in CRC [125,158,159]. The current gold-standard technique for CTC detection, the microscopic cell imaging, also presents many drawbacks such as the low number of markers, inability to analyze multiple markers simultaneously in routine use, long turnaround time (incompatible with the urgent need for delivery of treatment), and the requirements for specific laboratory instruments and professional expertise (pathologists) for data analysis [160,161]. Furthermore, the lack of large-population follow-up cohort studies increases the difficulties of translating current CSM-based CTC detection methods into the clinical setting for CRC screening, diagnosis, prognosis, real-time monitoring, and therapeutic response [50][51][52][53][54].…”