Cutting calories may improve response to cancer treatment

Restricting calories for a defined period of time may improve the success of cancer treatment, according to new research. The study offers valuable new data on how caloric intake may play a role in programmed cancer cell death and in the efficacy of targeted cancer therapies.

While previous studies suggest a connection between caloric intake and development of cancer, scientific evidence about the effect of caloric intake on the efficacy of cancer treatment has been rather limited to date. When fewer calories are consumed, the amount of nutrients available to the body's cells is reduced, slowing the metabolic process and limiting the function of some proteins. These characteristics of calorie restriction have led researchers to hypothesize that reducing caloric intake could potentially help inhibit the overexpression of the protein Mcl-1, an alteration associated with several cancers.

“While we know that consuming excess calories is associated with increased cancer risk, far less clarity exists in the scientific literature about how calorie restriction and the body's metabolism can potentially affect the body's response to cancer treatment,” said lead study author Jean-Ehrland Ricci, PhD, of the French Institute for Health and Medical Research in Nice, France. “By understanding the link between metabolism and the body's natural cancer suppressors and activators, we can perhaps improve the efficacy of therapy and improve survival for patients suffering from specific types of cancer.”

To better understand how calorie restriction might control the overexpression of Mcl-1 in certain cancers and consequently affect treatment efficacy, Ricci and a team of researchers conducted a series of experiments in mice that have developed lymphoma resembling Burkitt's lymphoma and diffuse large B-cell lymphoma. Their results were published in Blood (2013; doi:10.1182/blood-2013-01-478651).

The team began by separating the mice into two groups: regular diet and reduced-calorie diet (75% of normal intake). After one week on their designated diet, researchers then further divided the mice into four groups (two with regular diet and two with reduced calories) and treated them over the following 10 days either with the experimental targeted therapy, ABT-737, designed to induce cancer cell death and/or with no treatment. On day 17 of the experiment, both treatment and calorie restriction ended, and mice had access to as much food as they desired.

Neither treatment with ABT-737 nor calorie restriction alone increased the survival of mice over that of the other mice; however, the combination of ABT-737 and calorie restriction did. Median survival was 30 days in the control group that received a regular diet and no treatment, 33 days in mice that received a regular diet and treatment with ABT-737, 30 days in mice that received a reduced-calorie diet without treatment, and 41 days in mice that received a reduced-calorie diet and treatment with ABT-737. Shortly after this experimental period, investigators also observed that the combination of calorie restriction and ABT-737 reduced the number of circulating lymphoma cells in the mice, suggesting that the combination sensitized the lymphoma cells to treatment.
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