Cold Spring Harbor Laboratory Assistant Professor Jeremy Borniger highlighted the brain's critical role in sensing internal body signals, emphasizing that balance is essential for proper brain function. Neurons must operate in a coordinated manner; any disruption can have widespread consequences for brain activity.
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In mice studies, Borniger's team found that breast cancer interfered with the natural rhythm of stress hormone release, specifically corticosterone, which in humans corresponds to cortisol. Normally, these hormone levels fluctuate predictably throughout the day, but the presence of breast tumors flattened this rhythm, leading to consistently elevated corticosterone levels. This abnormality was associated with lower quality of life and increased mortality among the mice.
Disruptions to these daily rhythms are already known to contribute to anxiety and insomnia, conditions common among cancer patients. The regulation of these rhythms is managed by the HPA axis, comprising the hypothalamus, pituitary gland, and adrenal glands, which work together to maintain a healthy hormonal cycle.
Borniger's research revealed that changes in stress hormone rhythms occurred very early, even before physical tumors were detected. He noted a 40 to 50% reduction in corticosterone rhythm just three days after cancer induction, suggesting a significant early impact on the brain's stress regulation.
Further investigation showed that some neurons in the hypothalamus remained in a state of constant activity without signaling effectively. When researchers stimulated these neurons to restore a normal circadian pattern, the stress hormone rhythms normalized. This reset had a profound impact, allowing anti-cancer immune cells to migrate to breast tumors, which resulted in noticeable tumor shrinkage.
Borniger explained, "Enforcing this rhythm at the right time of day increased the immune system's ability to kill the cancer. If we do the same stimulation at the wrong time of day, it no longer has this effect."
The research team aims to understand how tumors disrupt normal physiological rhythms, with the hope that improving these rhythms can enhance the effectiveness of existing cancer treatments. Borniger stated, "We're focused on making sure the patient is physiologically as healthy as possible. That itself fights the cancer, potentially boosting the effectiveness of treatments while reducing their toxicity."