Cancer: Time of day may matter for diagnosis, treatment

The circadian rhythm is basically a master clock for the body.

Every day, the body goes through a cycle of processes that last for about 24 hours. This includes physical, behavioral, and mental changes, including hormonal activity and digestion. The circadian rhythm ensures the body goes through these processes.

Circadian rhythm also regulates the body’s sleep/wake cycle. During the day, the circadian rhythm helps us feel awake and alert. At night, it helps ensure the body rests through sleep.

Certain things can disrupt the body’s natural circadian rhythm, including:

If a person’s circadian rhythm becomes disrupted, they can have a circadian rhythm sleep disorder.

And previous studies in mice have linked disrupted circadian rhythm to cancer development.

In this study, the research team analyzed current data known about circadian rhythm and cancer development, diagnosis, and treatment.

The scientists found that metastasis — the spread of cancer cells from the original site to another area of the body — is connected to the circadian rhythm.

For example, the authors state, breast cancer is more likely to metastasize at night while a person is asleep, whereas prostate cancer is more likely to metastasize at other times during the day.

The authors believe that a person’s circadian rhythm could influence the effectiveness of chemotherapy and immunotherapy treatments. A process called chronotherapy can be used to coordinate treatment delivery with the body’s circadian rhythm.

Study researchers also found that the time of day a person receives cancer treatment may impact how successful it is.

The scientists cited a study in 2021 showing that people with melanoma who received immunotherapeutic drugs before 4:30 p.m. were almost twice as likely to survive as people who received the treatment later in the day.

The research team reported that the circadian rhythm might help doctors with cancer diagnosis.

As cancer cells make proteins at different times of the day, researchers believe that knowing when these proteins are at their highest concentration can help decrease misdiagnosis and help when performing biopsies.

After reviewing this study, Dr. Santosh Kesari, a neuro-oncologist and director of neuro-oncology at Providence Saint John’s Health Center, chair of the Department of Translational Neurosciences and Neurotherapeutics at Saint John’s Cancer Institute in Santa Monica, California, and regional medical director for the Research Clinical Institute of Providence Southern California, said this is a new concept that is not yet well understood.

Dr. Kesari, who was not involved in the research, told Medical News Today that, nevertheless:

“[B]ased on a variety of mostly preclinical data, and maybe some clinical data too, it seems like the circadian rhythm can have some profound effects, not just obviously on sleep and other functions, but a lot of biology in terms of cancers developing and also treating cancers and how the circadian rhythm can affect the effectiveness of the various treatments — immunotherapy and chemotherapy — that we give patients.”

Dr. Manmeet S. Ahluwalia, deputy director, chief scientific officer, chief of medical oncology, and Fernandez Family Foundation Endowed Chair in Cancer Research with Miami Cancer Institute, part of Baptist Health South Florida, who was also not involved in this study, weighed in on the argument.

He said that, if this concept is validated in a prospective setting, in the future it may help doctors recommend treatments at a particular time of the day to enhance efficacy or minimize side effects.

“For example, in patients with ovarian cancer who receive Adriamycin in the morning and cisplatin in the evening, they experience fewer side effects than patients who received Adriamycin in the evening and cisplatin in the morning,” he noted.

Both doctors agreed that additional research on this topic is needed before major changes are adopted.

“As the findings could have a far-reaching impact on how we treat our cancer patients, it would be great if the research related to circadian rhythm could be validated in a prospective clinical setting with translational research built-in to support the clinical findings,” Dr. Ahluwalia said.

Dr. Kesari cautioned that because cancer takes many years to develop in the body, it may be hard to study the impact of circadian rhythm on cancer development in humans.

Still, “I think there [are] some mouse models that can be studied to see disrupting [the] circadian rhythm and what it predisposes to,” he added.

With regards to circadian rhythm’s impact on cancer treatment, Dr. Kesari said that is really critical.

“The question is how big of an effect and is it really worth it to change whether we treat in the morning or afternoon or evening based on the circadian rhythm,” he stressed.

“I think there is a lot more to learn. And in particular, applying it to humans is going to be difficult, obviously, because the clinics are open 8 a.m. to 5 p.m. or 6 p.m. If it’s an IV chemo, then timing it in that context is not easy. Obviously, oral chemos or oral treatments can be done much easier at a specific time.”
— Dr. Santosh Kesari