Nature cell biologyAug 24, 2026

Daily body clock controls cancer cell particle release and may influence targeted treatment effectiveness

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 26, 2026

Abstract

The ctEV-CLOCK method achieves 12-hour resolution isolation of nascent circulating tumour-derived extracellular vesicles (ctEVs).

Circadian oscillations in ctEV abundance and functional properties were observed in multiple mouse tumour models.
Alterations in vesicle protein profiles varied depending on the time of day.
Synchronizing targeted therapy with peak ctEV protein abundance may significantly enhance therapeutic efficacy.
These findings suggest that ctEV circadian dynamics could play a regulatory role in tumour biology.

Simplified

Extracellular vesicles (EVs) are cell-derived nanoparticles that mediate intercellular communication, whereas circulating tumour-derived EVs (ctEVs) promote tumour progression. However, their circadian dynamics remain poorly understood owing to the lack of tools capable of resolving vesicle biogenesis dynamics. Here we introduce ctEV-CLOCK, a strategy enabling 12-h resolution isolation of nascent ctEVs. The method integrates metabolic glycoengineering-based timestamping with tumour-marker-guided selective click tagging, achieving enrichment of ctEV populations within defined time windows. Using this approach, we uncover circadian oscillations in ctEV abundance and functional properties across multiple mouse tumour models. These oscillations are accompanied by time-of-day-dependent alterations in vesicle protein profiles. Importantly, synchronizing targeted therapy with peak ctEV protein abundance markedly enhances therapeutic efficacy. Together, these findings position ctEV circadian dynamics as a regulatory layer in tumour biology and provide a framework for circadian-aligned cancer chronotherapy beyond immune-focused strategies.