Shanghai Researchers Examine Circadian Rhythms and Cancer Metastasis

The review highlights findings from various studies utilizing single-cell RNA sequencing, intravital imaging, and mechanistic experiments. It notes that epidemiological evidence links nighttime light exposure, shift work, chronic jet lag, and mutations in biological clock genes to an increased risk of cancer, particularly aggressive forms of breast and colorectal cancer. The International Agency for Research on Cancer categorizes circadian rhythm disruption as a Group 2A carcinogenic factor.

At various stages of metastasis, proteins related to the biological clock can impact processes such as epithelial-mesenchymal transition, the activity of enzymes that modify the extracellular matrix, and the characteristics of cancer stem cells. The authors also discuss connections between circadian mechanisms, macrophage states, cytokine networks, blood vessel formation, platelet activity, and the movement of tumor cells from the bloodstream into surrounding tissues.

The researchers stress the need for further studies that integrate serial single-cell sequencing, circadian proteomics, and intravital imaging. They argue that the same components of the biological clock may either inhibit or enhance metastasis, depending on the specific tumor type, stage of the disease, and time of day. If these findings are validated in clinical settings, they could lay the groundwork for chronotherapy, which involves timing chemotherapy, radiation therapy, or immunotherapy based on the tumor's vulnerabilities and microenvironment. Current research directions include compounds targeting BMAL1 and REV-ERB agonists, while agents affecting CRY1 have shown promising early preclinical results, although their safety and specificity require further scrutiny.