Tumor necrosis factor receptor superfamily member 10A and 10B (TRAIL-R1 and TRAIL-R2) (TRAIL-R1/R2)

TRAIL death receptors, specifically Tumor necrosis factor receptor superfamily member 10A (DR4) and 10B (DR5), are transmembrane proteins that initiate the extrinsic pathway of apoptosis upon binding to the TRAIL ligand. These receptors are characterized by an intracellular death domain that recruits the adaptor protein FADD and pro-caspases to form the death-inducing signaling complex (DISC), which subsequently activates effector caspases to execute cell death. They are considered promising therapeutic targets in oncology because they are often overexpressed on tumor cells while being minimally expressed or non-functional on normal cells, potentially allowing for selective tumor destruction. Various therapeutic agents, including recombinant human TRAIL and agonistic monoclonal antibodies, have been developed to target these receptors, though clinical success has been hampered by factors such as rapid drug clearance and tumor resistance. Current research is focused on developing next-generation agonists with enhanced clustering capabilities and exploring combination therapies to sensitize resistant tumors.

Other names

Death receptor 4Death receptor 5DR4DR5TNFRSF10ATNFRSF10BTRAIL receptor 1TRAIL receptor 2APO2KILLERTRICK2CD261CD262

Agonism of TRAIL death receptors (DR4 and DR5) triggers the extrinsic apoptotic pathway by recruiting FADD and pro-caspase-8/10 to form the death-inducing signaling complex (DISC), leading to caspase activation and cell death.