August 2023 | George M. Pikler, M.D., Ph.D., FACP

Cancer Chronotherapy

The trillions of cells in the human body have a biological clock, a circadian clock, an internal timepiece known as the circadian rhythm, where “circadian” stems from the Latin words “circa diem,” meaning “around a day.” This term explains how rhythmic fluctuations in roughly 24-h cycles in behavior and metabolism help the organism to adapt to and optimally respond to environmental changes and to organize and/or synchronize different biological and physiological processes to optimize its health.

Several lines of evidence support the idea that our circadian rhythm doesn’t just govern our sleeping schedule; it can also impact cancer development, diagnosis, and treatment. The exact mechanisms driving this link still need to be uncovered. Other research suggests that once cancer is present in the body, its ability to metastasize, appears to fluctuate in daily cycles and may be regulated by the circadian rhythm. Some cancers (breast) may be more likely to metastasize at night, while others (prostate and multiple myeloma) may be most likely to spread during the day.

There is currently an increasing interest in understanding the circadian rhythms of cancer cells and how this knowledge could be used in the diagnosis and treatment of cancer. Cancer cells produce proteins at different rates throughout the day, and some of these proteins are used as diagnostic molecular markers. We could decrease the chances of misdiagnosing a patient by collecting and testing biopsies at the time of the day when the concentration of these proteins is highest.

The practice of delivering medications, chemo, and immune therapies at specific times of day is known as chronotherapy. Clinical studies so far have confirmed that optimal timing of these therapies could decrease drug toxicity and increase treatment effectiveness. For example, in a recent study, melanoma patients who received immunotherapy infusions before 4:30 pm had nearly doubled overall survival times as compared with those patients who received the treatment later in the day. The optimal timing varies for different cancer types and therapeutics.

Not all studies of timed chemotherapy have had positive results. The clinical benefits of chronotherapy might be affected by factors such as the patient’s age, sex, and genetic background. Therefore, more research is needed to understand not only how these factors influence the optimal timing for cancer treatments but also how the circadian rhythm influences cancer progression at a genetic and cellular level.

Cancers (Basell) 2022 Oct; 14 (20): 5071
Trends in Cell Biology. 2023, March 24. 33 (9); 729-816
Erica

Erica Cross, PA

PA

Erica is a board certified Physician Assistant. She obtained her Master’s degree in Physician Assistant studies from Our Lady of the Lake College in Baton Rouge, LA. She began practicing in 2011 and has worked clinically in Orthopedics and Dermatology. The majority of her career has been spent in a Dermatology practice where she assisted in Mohs surgery, treating various types of skin cancer. She also teaches in the medical simulation department at the University of South Alabama and enjoys every aspect of medical education.