Table 1.

Main features of CTCs and ctDNA focusing on mCRC. Created with smart.servier.com

	CTCs	ctDNA
Origin	Viable and apoptotic cells	Mainly apoptotic cells
Components	DNA, RNA, proteins, metabolites	DNA
Suitable analyses	Genomics (mutations, copy number alterations, epigenetic alterations, fusion genes); transcriptomics (mRNA, including splice variants); proteomics; single-cell level analysis	Mutations, copy number alterations, epigenetic alterations, fusion genes
Culturing and xenografting	Yes	No
Sensitivity and specificity	Low sensitivity due to low abundance in plasma (especially for mCRC), heterogeneity of biomarkers for identification and EMT; around 50% sensitivity when combining CellSearch assay and the AdnaTest; variable specificity according to detection methods	High sensitivity due to large abundance in plasma (especially for mCRC); detection of mutant alleles with a fractional abundance up to 0.001% with dPCR; improved sensitivity and specificity with emerging tumor-informed techniques; impaired specificity due to background noise from non-neoplastic age-dependent alterations (i.e., clonal hematopoiesis)
Applications in the continuum of care for patients with mCRC	Prognosis, prediction of treatment response, molecular profiling, clonal evolution tracking and early identification of resistance mechanisms, treatment response monitoring, early detection of recurrence and MRD, in vivo tests of drug sensitivity	Prognosis, prediction of treatment response, molecular profiling, clonal evolution tracking and early identification of resistance mechanisms, treatment response monitoring, early detection of recurrence, and MRD

CTCs circulating tumor cells, ctDNA circulating tumor DNA, dPCR digital polymerase chain reaction, EMT epithelial-mesenchymal transition, mCRC metastatic colorectal cancer, MRD minimal residual disease, mRNA messenger RNA