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Effective cancer treatments follow the clock

Oncologists have long thought that cancer treatments tend to be more effective at certain times of day. But they have been unable to turn this knowledge into practice, because they did not understand the phenomenon well enough. Now, researchers have discovered a molecular mechanism that explains why sensitivity to anti-cancer drugs changes with the clock. They said their findings could lead to new drug treatments that may be more effective because they harness the power and precision of the body's internal clock.

The research team, which included senior author Joseph S. Takahashi, a Howard Hughes Medical Institute investigator at Northwestern University, and senior author Marina P. Antoch at the Cleveland Clinic Lerner Research Institute in Cleveland, Ohio, published its findings February 1, 2005, in the early online edition of the Proceedings of the National Academy of Sciences.

In experiments, which were conducted in mice, the scientists found that the body's internal biological clock affects the survival of immune cells that are targets of the anti-cancer drug cyclophosphamide (CY).

"We became interested in examining this issue because there is a long history of knowledge that chemotherapeutic agents produce different mortality and morbidity at different times of the day," said Takahashi. The initial experiments with normal mice, performed by Antoch during her tenure in Takahashi's lab, confirmed that animals treated with CY survived better when they received treatment in late afternoon than those whose treatments were initiated early in the morning. Antoch further extended these original findings after she moved to Cleveland and established her research program in the Department of Cancer Biology at the Cleveland Clinic Foundation.

To examine the mechanism for this difference, Antoch and her colleagues used mice that genetically lack different component
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
3-Feb-2005


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