Oncofetal chondroitin sulfate on tumor-derived extracellular vesicles: an emerging multivalent target for liquid biopsy

Circulating tumor-derived extracellular vesicles (tdEVs) offer a minimally invasive source of real-time molecular information from cancers. Detection of tdEVs, however, is hindered by their heterogeneity, scarcity, and lack of robust identification markers. Oncofetal chondroitin sulfate (ofCS), a placenta-associated glycosaminoglycan that is commonly re-expressed in cancer, has emerged as a promising, multivalent surface handle to recognize circulating tumor cells and proteoglycans in liquid biopsies. Recent work demonstrates that tdEVs released by diverse cancer cell lines and in plasma from patients with pancreatic cancer expose ofCS. This mini-review evaluates these findings and outlines priorities for clinical translation.