Cancer treatment - timing is everything

Research led by a cancer biologist at The Cleveland Clinic Lerner Research Institute has identified a molecular mechanism that links the body's internal clock to daily variations in how a patient responds to cancer treatment.

The findings could contribute to the development of more effective cancer treatment by using the body’s internal clock to determine the best time to administer drug therapies.

“These findings are significant as they provide the first mechanistic link between the biological clock system and the long-known phenomenon of daily variations in a patient’s response to different types of therapies,” said the study’s lead researcher, Marina Antoch, Ph.D., a cell biologist in The Cleveland Clinic Department of Cancer Biology. “The findings also provide the rationale for adjusting the timing of therapies to make them more efficient and less toxic.”

For some time, researchers have known that cancer treatments, including chemotherapy, can be more effective when administered at certain times of the day. However, this is the first time a molecular mechanism has been identified to explain why the body is more sensitive to anti-cancer drugs during certain time periods.

Dr. Antoch’s team also studied how the activity of some biological clock genes can modulate the body’s sensitivity to anti-cancer drugs and discovered that the process works by controlling the survival of immune B cells.

Results of the study led by Dr. Antoch and Joseph S. Takahashi, a Howard Hughes Medical Institute Investigator at Northwestern University, are available online in the Proceedings of the National Academy of Sciences. The paper will be published in the journal’s print edition at a later date.

Moving forward, the researchers will seek to understand the exact molecular signals sent from the body’s circadian rhythm to the immune system to look for useful drug targets and for drugs that can improve the effectiveness of therapies by manipulating the body’s internal clock.

The researchers will work in close collaboration with the laboratory of Andrei Gudkov, Ph.D., in The Cleveland Clinic Department of Molecular Genetics and with Cleveland BioLabs Inc., a Clinic spin-off company developing new therapies to decrease the harmful side effects of cancer treatments.