Drugs that inhibit mammalian target of rapamycin (mTOR) were shown to prevent radiation-induced tissue damage in mice by protecting normal stem cells that are crucial for tissue repair.
As explained in the study yielding these findings (Cell Stem Cell. 2012;11:401-414), mTOR plays a central role in the regulation of cell growth and cancer progression. However, increased mTOR activity can also cause certain cells to undergo changes that ultimately contribute to disease. mTOR activation is one of the most frequent events in head and neck squamous cell carcinomas (HNSCCs), malignancies that arise from the epithelial cells lining the oral mucosa, tongue, and pharynx. Use of the drug rapamycin, an FDA-approved mTOR inhibitor, has shown promising antitumor activity in several experimental models of HNSCC.
In the current project, researchers focused on the mucositis that develops in many persons with cancer who undergo radiotherapy or chemotherapy. This debilitating condition involves painful and deep mucosal ulcerations; tissue swelling in the mouth can leave patients unable to eat or drink, and may require them to use opioids to relieve the pain. Radiation can cause this condition by depleting normal stem cells that could repair damaged tissue.
As the investigators learned, rapamycin protects stem cells and extends their lifespan by preventing the accumulation of harmful molecules known as reactive oxygen species. Mice that received rapamycin during radiation treatment did not develop mucositis.
“Mucositis prevention would have a remarkable impact on the quality of life and recovery of cancer patients and at the same time would reduce the cost of treatment,” pointed out senior study author J. Silvio Gutkind, of the National Institute of Dental and Craniofacial Research in Bethesda, Maryland, in a statement describing his group’s work. “Our study provides the basis for further testing in humans, and we hope that these findings can be translated rapidly into the clinic.”