Résumé
The analysis of blood for circulating tumor cells (CTCs) called liquid biopsy has opened new avenues for cancer diagnostic and management, as well as the comprehension of the metastatic cascade [1]. As metastasis is responsible for about 90% of cancer deaths [2], it is of utmost importance to decrease the survival of CTCs, mostly to target specifically the metastasis-competent CTCs while they are reaching distant organs [3]. How CTCs are disseminating through the bloodstream? In advanced cancers, CTCs can travel as clusters or microemboli in the blood. CTCs traveling in a group seem to be released from hypoxic tumor regions [4] and clearly present a specific hypomethylation pattern related to stem cell features, underlying their higher aggressiveness [5]. Consequently, CTC clusters predict a poorer prognosis compared to single CTCs. Interestingly, CTC microemboli can also include other cell types, such as immune cells and/or cancer-associated fibroblasts from the tumor microenvironment, which have a higher capacity to survive and to metastasize. When CTCs are traveling the most? This specific question has already arised in 2020 when Cortés-Hernández et al. hypothesized that, because of evolutionary ecology reasons, malignant cells, including CTCs, should behave differently between day and night [6]. The recent work of Diamantopoulou et al. showed that the levels of CTCs increased at night in humans with breast cancer and mouse models of breast cancer and that CTCs in the rest-phase are more likely to metastasize [7]. This non-continuous generation of CTCs within the rest phase, if confirmed, will undoubtedly have major medical implications. However, key questions remain at this stage: Is it sleep and/or the circadian rhythm involved in the formation of CTCs and the metastatic spread of cancer, and by which specific mechanisms? The biology of most, if not all, living things is regulated by biological rhythms, in particular sleep and the circadian rhythm [8]. Due to the extreme diversity of cells typically generated in tumors, natural selection acting on cells, and/or groups of cells, may