Cancer and the circadian clock: has the time finally come?

W ithout the concept of time, there would be no physics, chemistry, or geology, but in medicine, time often gets short shrift. Yet in recent decades a small cadre of clinical investigators has found associations between the body's daily rhythms and the effectiveness of cancer treatment. Working in tandem, biologists have dissected the molecular underpinnings of the human circadian clock, a feedback loop that controls the sleep – wake cycle and coordinates physiological processes. Now a series of recent discoveries has implicated the circadian clock in cancer development, reinvigorating the fi eld of chronobiology, a subspecialty that has been operating at the fringes of cancer research. that highly cancer-prone mice missing the master tumor suppressor gene p53 lived 50% longer when a circadian clock gene called cryptochrome (Cry) was also deleted. In the study, published in February in the Proceedings of the National Academy of Sciences , the p53-mutant mice developed lymphomas and lymphosarco-mas and died by 19 weeks. By contrast, the mice missing Cry as well as p53 lived for a median of 28 weeks. These mice did eventually succumb to cancer, raising the question of whether the cancer was delayed or whether another protective system was activated. That question was answered, the researchers said, when skin fi bro-blasts isolated from the mice showed identical signs of onco-genic transformation, indicating that the mice missing Cry did not have delayed onset of cancer. Instead, they found that isolated cells from the p53-Cry – knockout mice were more sensitive to radiation-induced apoptosis, or programmed cell death. They concluded that eliminating the two genes had increased apoptosis, lengthening the animals ' lifespan by