Apo2L/TRAIL binding to DR4 and/or DR53, 4 initiates an intracellular signal cascade culminating in apoptosis.5 Apo2L/TRAIL pathway activation is efficacious in preclinical cancer models.6, 7, 8, 9, 10, 11 Unlike most normal cells, many tumor cell types are sensitive to Apo2L/TRAIL,12, 13, 14, 15, 16, 17 making the pathway attractive to anticancer therapeutic development. This evidence concerns the gene TNFSF10 and cancer.