Targeting TRAIL Death Receptors: TRAIL from the Lab to the Clinic

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) induces apoptosis upon ligation of its death domain-containing transmembrane receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) via activation of the extrinsic apoptosis pathway. Recombinant human (rh) TRAIL induces cell death in ˜ 50% of the cancers cell lines but not in normal cells. Apoptosis by rhTRAIL can be enhanced by DNA damaging drugs. Recently, DR4 and DR5-specific agonistic antibodies have been developed. In addition, several death receptor-selective TRAIL variants were generated using computational design. Platinum-based chemotherapy is u…