ZÜRICH, Switzerland — The time at which doctors administer chemotherapy drugs influences how well they fight cancer, a new study explains. Scientists in Switzerland say some treatments work better during the day, while others are more effective at night. The phenomenon could lead to personalized treatments for cancer patients. It also has implications for the study of tumor growth and diagnosis.
Most living organisms – animals, plants, fungi, and even bacteria – have an internal clock, which scientists call circadian rhythms. It orchestrates the biochemical, physiological, and behavioral functions in each cell according to a 24-hour cycle. The rhythms don’t just govern sleeping schedules, they can also impact the development of disease.
“The circadian rhythm governs most of the cellular functions implicated in cancer progression, and its exploitation therefore opens new promising directions in the fight against metastasis,” study authors write in the journal Cell Biology.
Stopping cancer’s spread, or metastasis, would be the “Holy Grail” of cancer research — turning it from a fatal to more of a chronic disease. Our circadian rhythms help synchronize gene expression, immune function, and cell repair. However, disruptions by erratic sleep, jet lag, or shift work display a link to life-threatening illnesses, including cancer.
They can also fuel migration of cells, leading to the formation of secondary tumors that often kill patients. For that process to occur, cells need to break away from the primary tumor, enter the bloodstream, and infiltrate another organ.
Some cancers only spread when you’re asleep
Studies have shown the rate at which this happens changes throughout the day, but the timing differs between cancer types. For example, breast cancer is more likely to spread at night, while we are usually asleep, whereas prostate cancer and multiple myeloma peak at other points during the day. Leveraging this information would enable chemo and immunotherapies to begin at the optimal hour — a practice researchers call chronotherapy.
“Circadian rhythm-based metastasis formation should be seen as an opportunity to intervene in the most timely and effective way,” the study authors explain. “Chronotherapy holds promise to be a valuable alternative treatment option in the fight against cancer.”
Clinical trials have shown chronotherapy also reduces the severity of side-effects experienced by patients, which can impact the success of each treatment. The researchers cited a recent study in which survival rates almost doubled in melanoma patients given immunotherapeutic drugs before 4:30 p.m. This was compared to those who received the treatment later in the day.
The best timing varies for different cancer types and therapeutics. Clinical benefits of chronotherapy might also depend on factors such as the patient’s sex and genetic background. Knowledge of the circadian rhythms of cancer cells could also aid cancer diagnoses. Cancer cells produce proteins at different rates throughout the day.
Some of these proteins serve as diagnostic molecular markers. Doctors 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.
“More mechanistic understanding of these processes will be required to fully unleash its potential on the clinical side,” study authors from the Swiss Federal Institute of Technology conclude.
“Defining the circadian-rhythm-controlled timing of proliferation and release of circulating tumor cells into the bloodstream in additional cancer types may help to identify the optimal time window for therapy administration.”
South West News Service writer Mark Waghorn contributed to this report.