Tumor necrosis factor receptor superfamily member 10B (DR5) (DR5)

Tumor necrosis factor receptor superfamily member 10B (DR5), also identified by the sequence code PRO95780 in specific therapeutic contexts, is a transmembrane protein that mediates apoptosis (UniProt O14763). As a member of the TNF receptor superfamily, DR5 contains a cytoplasmic death domain that, upon activation by its ligand TRAIL (TNF-related apoptosis-inducing ligand), recruits FADD and caspase-8 to initiate the extrinsic apoptotic pathway (PubMed: 25100311). DR5 is highly expressed in a variety of solid and hematologic malignancies compared to normal tissues, which has led to its investigation as a target for pro-apoptotic cancer therapies (NIH: PMC6010343). Therapeutic strategies include the use of agonistic monoclonal antibodies, such as Drozitumab (Apomab), and recombinant TRAIL variants designed to trigger tumor cell death (ClinicalTrials.gov). However, clinical development has faced challenges including dose-limiting hepatotoxicity and intrinsic or acquired resistance in tumor cells (PubMed: 30655458). Current research is focused on next-generation multivalent agonists and combination regimens to enhance efficacy and overcome these safety concerns.

Other names

TRAIL receptor 2TRAIL-R2TNFRSF10BCD262KILLERTRICK2Death receptor 5PRO95780

Agonist binding to DR5 induces receptor clustering and formation of the death-inducing signaling complex (DISC), leading to activation of caspase-8 and subsequent apoptosis.