“…At present, various technologies are developed for CTCs isolation, however, they are mainly used for research purposes rather than clinical applications (Bankó et al, 2019). Among the obstacles are the presence of ITH (Levitin et al, 2018;Lim et al, 2019), limited knowledge on CTCs mechanism of action in cancer progression (shedding from the primary/metastasis tumor, survival in bloodstream, avoidance of apoptosis, colonization potentials and settlement in distant organs), the rarity of CTCs (0 to 10 CTCs/ml whole blood in 30% to 50% mCRC patients) (Zieglschmid et al, 2005), various sizes of CTCs and the lack of clinical validation (Millner et al, 2013;Rejniak, 2016;Kowalik et al, 2017;Bankó et al, 2019). In addition, there are only a few studies relating to CTCs pharmacogenomics and underlying survival mechanisms (Wang et al, 2018) as well as the cell-cell interactions in CRC microenvironment (Krog and Henry, 2018), and majority of them are based on experimental and theoretical extrapolations (Burz et al, 2018).…”