Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (TNFSF10)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as TNFSF10, is a type II transmembrane protein and a member of the TNF superfamily that plays a vital role in immune surveillance and the induction of programmed cell death (UniProt P50591; NCBI Gene 8743). It is naturally expressed on the surface of immune effector cells, such as Natural Killer (NK) cells and cytotoxic T lymphocytes, where it interacts with pro-apoptotic death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) on the surface of target cells (Frontiers in Oncology, 2019). This binding triggers the assembly of the death-inducing signaling complex (DISC), leading to the activation of caspase-8 and the subsequent extrinsic apoptotic pathway (Journal of Clinical Investigation, 2014). A defining characteristic of TRAIL is its ability to selectively induce apoptosis in malignant cells while sparing most normal cells, making it a highly attractive target for oncology therapeutics. Drug development efforts have focused on recombinant human TRAIL (e.g., dulanermin) and agonistic monoclonal antibodies targeting DR4 or DR5 to mimic this natural immune mechanism (ClinicalTrials.gov). However, clinical progress has been hindered by the short half-life of TRAIL-based agents and the development of resistance in tumors through mechanisms such as the upregulation of decoy receptors (DcR1, DcR2) or anti-apoptotic proteins like c-FLIP.

Other names

TRAILTNFSF10APO2LCD253TL2Apo-2 ligand

Agonism of death receptors DR4 and DR5 to induce the extrinsic apoptotic pathway via caspase-8 activation.