The Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Lung Cancer Still Following the Right TRAIL?

Tumor necrosis factor-related apoptosis-inducing ligand is a type II membrane-bound protein whose C-terminal extracellular domain shows clear homology to other tumor necrosis factor family members. It is constitutively expressed on macrophages, T cells, natural killer cells, and dendritic cells and selectively kills transformed cells leaving most of the normal cells alone. This selectivity has led to great interest in it use as a therapeutic agent for the treatment of malignancy. In this review, this critical pathway is described, highlighting its mechanistic manipulation for therapeutic benefit and the recent phase I and II trials in lung cancer that have been performed or are currently ongoing are also discussed.