Table 1.

Comparison of “Classic” tumor markers and “New” liquid biopsy analytes.

Liquid biopsy field
“Classic” tumor marker(s)		“New” liquid biopsy analyte(s)
• CA 27.29 • CA 19-9 • CA15-3 • CA 125 • PSA • NSE • CEA • AFP	• Strength    ✓High level with progressive disease    ✓Decrease rate with remission    ✓Simple procedure    ✓Easily obtainable specimens    ✓Minimal invasive    ✓Currently using in clinic • Limitation    ✓Lack of specificity and sensitivity    ✓Detectable in benign and healthy conditions    ✓Do not provide information related to the metastatic cascade    ✓High level only in large tumor volumes	• CTCs • ctDNA • TEPs • EVs	• Strength    ✓Cancer specific    ✓Simple procedure    ✓Easily obtainable specimens    ✓Minimal invasive    ✓Genome, transcriptome, proteome and secretome evaluation    ✓Related with metastasis cascade    ✓Informative for cancer heterogeneity    ✓Monitoring drug response and resistance therapy    ✓High specificity and sensitivity • Limitation    ✓Not completely validate and/or utilize in clinic    ✓Lack of standardize and integrated method for detection

Circulating analytes, such as CTCs, ctDNA, TEPs, and EVs, are already part of the liquid biopsy, and classical tumor markers also could be included. Indeed, they can be detected in serum, and the combination of classical tumor markers with circulating analytes (e.g., ctDNA) can be used to develop a multi-analyte blood test (30) as a screening method for early tumor detection.

* AFP, Alfa fetoprotein; CA, Carbohydrate antigen; CEA, Carcinoembryonic antigen; PSA, Prostate-specific antigen; NSE, Neuron specific enolase; CTC, Circulating tumor cells; CtDNA, Circulating tumor DNA; TEPs, tumor-educated platelets; EVs, Extracellular vesicles.