Fixing disrupted body clock rhythms found to lower cancer risk: Study

Every cell in the body follows a circadian rhythm, a 24 hour biological cycle that aligns behavior, metabolism, and hormone production with day and night. This rhythmic balance is controlled by a communication network called the hypothalamic pituitary adrenal (HPA) axis, which regulates secretion of the stress hormone corticosterone (the counterpart of cortisol in humans). Chronic disruption of these cycles-through stress, poor sleep, or diet—has long been associated with metabolic and immune dysfunction.

To explore how cancer interferes with this system, the researchers developed a mouse model of breast cancer and closely monitored corticosterone levels around the clock. Within just three days of inducing the cancer, even before tumors were physically detectable, corticosterone rhythms were cut in half, showing blunted day night variation. When the scientists examined the brain’s hypothalamus, they found that crucial rhythm generating neurons had become hyperactive yet low output, disrupting their ability to send proper timing signals.

Using chemogenetic technology, the team selectively stimulated these hypothalamic neurons at different times of day. Remarkably, when they activated the neurons at a specific circadian window—just before the light to dark transition—the mice’s hormonal rhythms returned to normal. This re synchronization of corticosterone release strengthened anti cancer immune responses, increasing tumor infiltrating T cells and causing tumors to shrink significantly. But when neuron activity was restored at the wrong time of day, the effect disappeared, underscoring how tightly linked circadian timing is to cancer control.

The results suggest that synchronizing biological clocks—through “chronotherapy” or timed treatment—could enhance existing cancer treatments while lowering their toxicity. Future research will explore exactly how tumors disrupt circadian communication and whether similar strategies can be adapted for human cancers.

REFERENCE: Sahar, S., Sassone-Corsi, P. Metabolism and cancer: the circadian clock connection. Nat Rev Cancer 9, 886–896 (2009). https://doi.org/10.1038/nrc2747