mTOR Inhibition for the Prevention of Epithelial Stem Cell Loss and Mucositis

Description:

The integrity of the epidermis and mucosal epithelia is highly dependent on self-renewing stem cells and, therefore, is vulnerable to physical and chemical damage from common cancer treatments, such as radiation or chemotherapy. Consequently, many cancer patients undergoing these treatments develop mucositis, a debilitating condition involving painful and deep mucosal ulcerations. Since current prevention and treatment options for mucositis are limited, providing only minor relief and no protection to stem cells, novel therapies are needed.

The NIH inventors have recently discovered that the mammalian target of rapamycin (mTOR) mediates stem cells exhaustion in the skin and leads to progressive hair loss. More importantly, they have shown that mTOR inhibition reduces oxidative stress in the epithelial stem cells and mTOR inhibitors can be used to increase the re-populative capacity of tissue resident stem cells to maintain tissue homeostasis after injury or stress. Therefore, this technology could be used to prevent epithelial stem cell loss and provide relief from radiation-induced mucositis. Likewise, it could be used to prevent mucositis and hair loss in patients undergoing chemotherapy and stem cell transplantation. For optimal delivery and effectiveness, rapamycin or other mTOR inhibitor could be administered in the form of a mouthwash or gel product to patients prior to receiving radiation (or other) treatments.