Rapamycin may prevent radiation-induced mucositis

2012 09 10 13 35 26 581 Dry Cracked Soil 70

Research scientists from the U.S. National Institute of Dental and Craniofacial Research have discovered a drug that protects stem cells and could prevent cancer patients from developing radiation-induced oral mucositis.

The group found that the drug rapamycin appeared to prevent radiation-induced tissue damage in mice by protecting normal stem cells that are crucial for tissue repair. Although this study was preclinical, rapamycin has already been cleared by the U.S. Food and Drug Administration and is currently in clinical trials (Cell Stem Cell, September 7, 2012, Vol. 11:3, pp. 401-414).

Ramiro Iglesias-Bartolome, a postdoctoral fellow specializing in cell biology at the National Institutes of Health's Oral and Pharyngeal Cancer Branch, and colleagues were initially trying to determine if the addition of a class of drugs known as mammalian target of rapamycin (mTOR) inhibitors might sensitize head and neck cancer.

What the researchers did discover was that the mTOR inhibitor rapamycin protects stem cells taken from the mouths of healthy individuals from radiation-induced death and DNA damage. The drug extended the life span of these normal stem cells and allowed them to grow. Rapamycin exerted these protective effects by preventing the accumulation of harmful molecules called reactive oxygen species (ROS).

Mice that received rapamycin during radiation treatment did not develop mucositis. Specifically, the rapamycin treatment on mice was effective at limiting the loss of proliferative basal oral epithelial stem cells upon irradiation, thereby enhancing their tissue repopulating capacity and preventing the appearance of ulcers.

In a commentary on the research, Toren Finkel, PhD, from the National Heart, Lung, and Blood Institute, acknowledged that systematic rapamycin use is known to cause significant toxicities (Cell Stem Cell, September 7, 2012, Vol. 11:3, pp. 287-288). He suggested, however, that it might be possible to develop a mouthwash or gel that could regulate the levels of ROS, preserve the tissue-repopulating capacity of the epithelial stem cells, and provide targeted relief from radiation-induced mucositis.

Reduction or prevention of mucositis could have profound impact, not only with respect to the cost of treating the condition, but also enabling patients to complete their treatment. Clinical studies have repeatedly documented that some patients do not complete their chemotherapy and/or radiation therapy treatments when they develop this condition.

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