Can Chronotherapy Improve Mesothelioma Treatment?
June 7, 2018
The science of chronotherapy generally involves helping people maintain a healthy sleep schedule.
Some researchers believe biological clocks may also hold a key to optimizing chemotherapy.
“Chronochemotherapy” is an experimental technique that aligns treatment with the circadian rhythm of cancer cells. It could make chemotherapy for mesothelioma more effective while also reducing drug side effects.
Every cell has a biological clock that determines when it is most and least vulnerable to DNA damage. The biological clocks of cancer cells are often out of sync with the rest of the body’s circadian rhythm. Exploiting this misalignment may be a way to make chemotherapy more effective.
Chronochemotherapy is not a new idea, but recent advances in technology have brought scientists closer to unlocking its potential.
Circadian Rhythm and Cancer
Every cell in the body has its own biological clock. The brain keeps all these cellular clocks synchronized by releasing hormones.
These biological clocks regulate the body’s circadian rhythm, which affects the way it works at different times of the day.
Your circadian rhythm helps you wake up in the morning and fall asleep at night. At the microscopic level, the circadian rhythm tells cells when to focus on different activities.
Cancer researchers are particularly interested in the timing of DNA repair. Many chemotherapy drugs are designed to damage cancer-cell DNA, causing cancer cells to break down.
But if chemotherapy is given during the time when cancer cells are repairing their DNA, the drugs are not as effective.
Chronochemotherapy: Timing Treatment Right
Chronochemotherapy is based on the idea that giving chemotherapy at certain times could improve outcomes for cancer patients.
So far this approach is not proven to increase drug effectiveness, but some research shows it can reduce side effects.
Researchers have known for decades that cancer cells often have altered circadian rhythms. For example, tumor cells may be 12 hours off, doing their nighttime activities during the day and their daytime activities at night.
Because of their altered biological clocks, cancer cells often perform their DNA repairs at a different time than the rest of the body.
The goal of chronochemotherapy is to administer cancer drugs when the body’s healthy cells are repairing their DNA but cancer cells are not.
Timed this way, chemotherapy drugs should do more damage to cancer cells and less collateral damage to healthy cells.
A 2017 study in Radiation Oncology reported a phase II trial of chronochemotherapy for patients with nasopharyngeal carcinoma. The experimental group experienced fewer side effects than patients who received standard chemotherapy, but overall survival was the same for both groups.
New Research Tools Reveal Workings of Biological Clocks
Scientists have been aware of the circadian rhythm for a long time, but it is difficult to figure out exactly how biological clocks work.
Chronochemotherapy researchers believe this is why the technique is not yet reliable.
In May 2018, scientists at the University of North Carolina reported a new research method that could lead to a breakthrough. Researchers were able to measure DNA-repair activity over a whole 24-hour period in mice treated with the drug cisplatin.
Cisplatin is one of the most common chemotherapy drugs used in mesothelioma treatment. This research should help specialists understand how cisplatin affects mesothelioma cells at different times in their circadian rhythm.
Remaining Challenges of Chronochemotherapy
Doctors have pointed out practical issues with scheduling chemotherapy according to a tumor’s broken clock.
What if it turns out the best time to give chemotherapy is in the middle of the night? Disrupting a patient’s sleep schedule could do more harm than good.
One proposed solution is to design an automatic chemotherapy pump patients can take home with them. If chemotherapy needs to be administered in the middle of the night, patients could be connected to the pump when they go to bed. Then the pump would deliver the drug at the set time.
Another solution under investigation is to use a special drug to reset the biological clocks of cancer cells. This way, doctors would be able to make chronochemotherapy as convenient as possible for the patient.
Researchers around the world are exploring these possibilities, so it is only a matter of time before mesothelioma specialists understand the impact chronochemotherapy can have.