Further, the use of recombinant human TRAIL in humans is safe and was well-tolerated in phase I and II clinical trials; however, objective clinical responses were rare and with no antitumor responses in patients with colon cancer.8,13,14 We and others have investigated mechanisms to overcome the known and highly prevalent causes of TRAIL resistance;15,16 however, the clinical trials highlighted the current limitations of TRAIL’s clinical use as a single agent. This evidence concerns the gene TNFSF10 and malignant colon neoplasm.