New research could improve a well-known side effect of chemotherapy and improve patient quality of life post treatment

Most living beings cycle through daily rhythms in cellular, physiological and behavioral phenomena that are determined by internal clocks. Research shows that disruption or alterations to these internal clocks, or regulators, are associated with many illnesses and diseases. What has remained unclear, is how interventions and treatments for illness and disease, such as chemotherapy, impacts internal clocks during and after treatment.

Cancer patients often experience behavioral side effects after treatment, such as fatigue and anxiety. Biological factors such as disruptions in the circadian rhythms of hormones often coincide.

New research out of The Ohio State University Institute for Behavioral Medicine Research demonstrates that repeated administrations of chemotherapy disrupt both central and peripheral circadian rhythms and are associated with worse and enduring disruptions in cancer patients’ locomotor activity rhythms.

Leah Pyter, PhD, associate professor of Psychiatry and Neuroscience at The Ohio State University College of Medicine and Institute for Behavioral Medicine Research, says these findings support the possibility that targeted circadian realignment therapies may be a novel and noninvasive way to improve patient outcomes during and after chemotherapy.

“This is significant because the circadian master clock in the brain controls the timing of cell functions throughout the entire rest of the body,” says Pyter.

Pyter and a team of fellow Ohio State researchers’ examination of the effects of chemotherapy on molecular, physiological, and behavioral circadian rhythms was just published in the journal Brain, Behavior, and Immunity.

Prior to this study, this group previously reported that solid tumors alter time-of-day fluctuations in clock gene expression using a mouse model of breast cancer. For this study, they built on that model to examine the extent to which paclitaxel, a common chemotherapy drug used for breast and other cancers, altered circadian rhythms and dampened the amplitude of clock gene expression, genes that participate in regulatory feedback loops that oscillate with circadian rhythms, in the brain and adrenal glands of tumor-free mice.

They found that paclitaxel disrupts clock gene rhythms in the suprachiasmatic nucleus (master clock), which is in the hypothalamus, the area of the brain that manages the pituitary gland and the autonomic nervous system. They also found that paclitaxel also disrupts clock gene activity in other brain regions and adrenal glands, which are associated with chemotherapy-induced inflammation. These findings align with a previous study that demonstrates that 5-fluorouracil chemotherapy, which works through different antineoplastic mechanisms compared to paclitaxel, also blunts the amplitude of circadian rhythms.

The convergent findings suggest how the disruption of circadian rhythms impact cortisol release that correlates with reduced quality of life and decreased long-term cancer survival rates.

“This has the potential to impact patient health long after treatment,” Pyter says. “My vision is to create a clinic for cancer survivors to provide continued care to help them deal with the aftermath of cancer.”