Biological perspectives on circadian cancer therapy.

Temporal coordination of biologic processes with an approximately 24-hour cycle (circadian) is ubiquitous throughout the animal and plant kingdoms. In each organism studied, the capability to keep biologic time is an inherited characteristic. These biological clocks anticipate, get the organism ready for, regular environmental changes. The immense selective environmental pressure to keep time accurately is reflected in the parallel evolution of different molecular strategies for biologic timekeeping that have apparently arisen independently several times throughout evolution. The anatomic, biochemical, and molecular mechanisms of the clock are currently being defined. Circadian temporal organization at the cellular, organ, and organismic levels results in predictable differences in the capacity of plants, animals, and human beings to respond to therapeutic interventions administered at different times throughout this daily cycle. The biologic basis for these time-of-day differences in therapeutic outcome derive from the circadian dependence of drug pharmacology and the circadian physiology of both normal and malignant tissues. In the treatment of cancer, circadian timing of anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, enhanced tumor control, and improved host survival. The routine clinical application of such principles is facilitated by the availability of programmable drug delivery devices.