Mice that had been genetically engineered to produce a protein known as Smad7 in the surface layers of the oral cavity were dramatically more resistant to the development of radiation-induced oral mucositis than were controls, researchers reported in Nature Medicine.
Currently, there is no FDA-approved treatment for oral mucositis, which develops in 40% to 70% of persons who undergo upper-body radiation treatment for cancer. Some patients develop mouth sores so severe that feeding tubes are needed for nutrition and narcotics are needed for pain relief.
Xiao-Jing Wang, PhD, of the University of Colorado Cancer Center in Denver, Colorado, and colleagues found that Smad7 protects against or heals these ulcers. The protein dampened two pathways known to contribute to oral mucositis, and promoted the migration of oral epithelial cells to close the wound.
In addition to administering Smad7 by means of genetic engineering, the researchers explored topical use of the protein. The team used cultured bacteria to produce a combination protein of Smad7 and a short peptide that was able to cross through cell membranes. When this compound was applied directly to the oral cavity in mice, the compound protected against the development of oral mucositis and even worked to heal existing ulcers. Notably, the topical treatment revived wounded normal cells but not cancer cells, avoiding a major problem presented by the growth factors that are currently used to promote ulcer-healing cell growth.
“It’s very reasonable to hope that this line of research will result in a drug that patients can self-administer topically to oral mucositis sores, or use to prevent them altogether, thus significantly improving the quality of life for many cancer patients,” observed Wang in a statement issued by the University of Colorado Denver.