TNFSF10

Tumor Necrosis Factor Superfamily Member 10 (TNFSF10), commonly termed TRAIL (TNF-related apoptosis-inducing ligand) or APO2L, is a type II transmembrane protein that selectively induces apoptosis in transformed cells by binding to death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2). Its activation triggers caspase cascades via the extrinsic apoptotic pathway, while decoy receptors (DcR1/DcR2) modulate this activity in normal tissues. TRAIL signaling intersects with JNK and NF-κB pathways, influencing inflammation and cell survival under specific contexts. Dysregulation of TRAIL pathways is implicated in cancer immune evasion, neurodegenerative disorders, and autoimmune diseases like rheumatoid arthritis. Despite early promise, clinical trials of recombinant TRAIL (Dulanermin) and DR4/DR5 agonists (Conatumumab, Tigatuzumab) showed limited efficacy due to tumor resistance and systemic toxicity. Current strategies focus on sensitizing agents (e.g., proteasome inhibitors) and bispecific antibodies to overcome resistance. TRAIL-based gene therapies and nanoparticle delivery systems are under preclinical exploration to enhance tumor targeting.