Identification of a non-traditional pathway for spiriting a cancer-promoting protein into the cell nucleus points to a possible combination therapy for esophageal cancer and indicates a mechanism of resistance for new drugs that attack the Hedgehog pathway, the traditional (or canonical) path of cancer-promoting proteins into cells. A team of researchers at The University of Texas discovered that the mTOR molecular pathway promotes the activity of the Gli1 protein in esophageal cancer development and progression. According to senior author Mien-Chie Hung, clear-cut mechanism has been shown to link all non-canonical activation of Gli1 through a single pathway, TOR. The experiments showed a combination of the mTOR inhibitor RAD-001 (Everolimus®) and the Hedgehog inhibitor GDC-0449 (Erivedge®) steeply reduced the tumor burden in a mouse model of esophageal adenocarcinoma.