AuthOr’s VIew

For many years cell death was studied with far less interest than other basic cellular processes such as proliferation and differentiation. As it was thought that cell death was simply a degenerative phenomenon produced by injury, the idea that cell death would also occur as a genetically controlled event in healthy animals did not gain wide acceptance. It is now clear that failure or suppres-sion of apoptosis likely contributes to the initial development of cancer and to the appearance of tumor cells resistant to cytotoxic therapy. Over the years, a variety of drugs have been developed to kill tumor cells by inhibiting some com-ponent of key biomolecular pathways that contribute to uncontrolled tumor growth. Many of these drugs have lim-ited specificity for tumor cells, so the potential for drug-induced death of nor-mal cells is increased. In 1995, Wiley et al. described the selective tumoricidal activity of a (then) newly identified member of the TNF superfamily— TNF-related apoptosis-inducing ligand (TRAIL).1 Since that initial paper, there have been numerous reports examin-ing the direct tumoricidal activity of TRAIL (alone or in combination with a wide variety of drugs). Most of these studies have used recombinant TRAIL, but there has been considerable interest Activation of systemic antitumor immunity via TRAIL-induced apoptosis Britnie r. James1 and thomas s. Griffith1,2,3,