Time of day matters when it comes to cancer diagnosis and treatment

“The circadian rhythm governs most of the cellular functions involved in cancer progression, and therefore its exploitation opens promising new directions in the fight against metastasis,” write the authors, molecular oncologists Zoi Diamantopoulou, Ana Gvozdenovic and Nicola Aceto from ETH Zurich in Switzerland.

Our circadian rhythms help our bodies synchronize different tasks throughout the day, including gene expression, immune function, and cellular repair. We’ve long known that chronically disrupted circadian rhythms – due to erratic sleep, jet lag or shift work, for example – can predispose us to a number of health conditions, including cancer. More recent work has shown that circadian rhythms are not only involved in tumor initiation, but also govern cancer progression and metastasis, the colonization of secondary sites in the body.

Metastases are the leading cause of death in cancer patients. For metastasis to occur, cells must break away from the primary tumor, enter the bloodstream, and then travel and infiltrate a new organ. Studies have shown that the rate at which cancer cells break away from the primary tumor and enter the bloodstream oscillates rhythmically throughout the day, but the timing of this rhythm differs between cancer types. For example, breast cancer is more likely to metastasize at night while we sleep, while prostate cancer and multiple myeloma peak at other times of the day.

The authors argue that we could leverage this information when administering chemotherapies and immunotherapies to target tumor cells at the optimal time. The practice of administering medications and immune therapies at specific times of the day is known as chronotherapy.

“Circadian rhythm-based metastasis formation should be viewed as an opportunity to intervene in the fastest and most effective way,” the authors write. “Chronotherapy promises to be a valuable alternative treatment option in the fight against cancer.”

Clinical studies have shown that chronotherapy can reduce the severity of side effects experienced by patients and can also impact the effectiveness of treatment. For example, the authors describe a recent study in which melanoma patients who received immunotherapeutic drugs before 4:30 p.m. were almost twice as likely to survive as patients who received the treatment later in the day. The optimal timing varies between cancer types and treatments, and the authors also note that the clinical benefits of chronotherapy could be affected by factors such as the patient’s gender and genetic history.

Knowing the circadian rhythms of cancer cells could also help in cancer diagnosis. Cancer cells produce proteins at different rates throughout the day, and some of these proteins are used as diagnostic molecular markers. We could reduce the risk of misdiagnosing a patient by taking and testing biopsies at the time of day when the concentration of these proteins is highest.

“A more mechanistic understanding of these processes will be needed to fully unlock its clinical potential,” the authors write. “Defining the circadian-controlled timing of proliferation and release of circulating tumor cells into the bloodstream in other types of cancer can help identify the optimal time window for treatment delivery.”