Science

Timed meals and chemo may boost anti-cancer therapy

Last Updated: 2006-04-27 15:51:22 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - A team of scientists has demonstrated, for the first time to their knowledge, endogenous circadian rhythmicity in a primary tumor. The discovery might open up new treatment approaches to chronomodulated therapy -- adjusting the temporal pattern of drug delivery to improve the toxic-therapeutic ratio.

The team's studies also suggest that tumor rhythms are sensitive to temporal changes in feeding. "Perhaps by combining chronotherapy with treatments (such as restricted feeding) that can manipulate the phase of the tumor and the host rhythms, the benefits of this treatment approach can be further enhanced," lead scientist Dr. Alec J. Davidson told Reuters Health.

Using transgenic rats, Dr. Davidson, from the Morehouse School of Medicine in Atlanta and colleagues at the University of Virginia in Charlottesville, studied expression patterns of the circadian clock gene (Period 1) in hepatocellular carcinoma and adjacent normal liver tissue.

"This animal's tissues express firefly luciferase in proportion to Per1 gene expression, allowing us to measure molecular rhythms by merely recording light emission with very sensitive detectors," Dr. Davidson explained.

"This comparison revealed not only alterations in the tumor rhythms -- the clock ran faster in the isolated tumor than in healthy liver tissue -- but also that a robust clock still exists in the tumor," Dr. Davidson said.

To study the effects of restricted feeding on the circadian rhythms of liver tumors, hepatoma-bearing rats were fed ad libitum, or a single small meal at night, or the same meal during the day.

"Temporally restricting food availability to either day or night altered the phase of the rhythms in both healthy and malignant tissue," the scientists report in the April 1st issue of the International Journal of Cancer. However, the tumors were much less sensitive to the restricted feeding signal "resulting in markedly different phase relationships between host and tumor tissue as a function of mealtime."

In the night-fed rats, the tumors rhythms peaked earlier than the healthy liver, and in the day-fed rats, the tumors peaked later than the healthy liver.

"Because circadian clocks are known to modulate the sensitivity of many therapeutic cytotoxic targets, controlling meal timing might be used to increase the efficacy of treatment," the authors suggest. "Specifically, meal and treatment schedules could be designed to take advantage of coincident times of greatest tumor sensitivity and lowest sensitivity of host tissue damage."

Int J Cancer 2006;118:1623-1627.