Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) (TNFRSF10B)

Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), widely known as Death Receptor 5 (DR5), is a key mediator of the extrinsic apoptotic pathway (UniProt: O14763). It is a type I transmembrane protein characterized by an extracellular cysteine-rich domain and an intracellular death domain. Upon binding to its cognate ligand, TRAIL (TNFSF10), the receptor undergoes trimerization and recruits the Fas-associated death domain (FADD) and pro-caspase-8 to form the death-inducing signaling complex (DISC) (NCBI Gene: 8795). This activation leads to a caspase cascade that results in programmed cell death. In oncology, TNFRSF10B is a highly prioritized target due to its preferential expression on the surface of various tumor cells compared to healthy tissues. Therapeutic efforts have focused on developing DR5 agonists, such as monoclonal antibodies (e.g., conatumumab) and recombinant TRAIL variants, to selectively eliminate cancer cells (PubMed: 30232147). However, clinical development has encountered hurdles including intrinsic resistance and suboptimal receptor clustering, prompting the design of next-generation multivalent and bispecific agents like INBRX-109 and ABBV-621. The mRNA of TNFRSF10B is also a subject of study for its regulation by p53 and its potential as a biomarker for treatment response.

Other names

Death receptor 5DR5TRAIL receptor 2TRAIL-R2CD262KILLERTRICK2TRICKBZTNFR9

Agonism of the receptor to induce trimerization and formation of the death-inducing signaling complex (DISC), leading to caspase activation and extrinsic apoptosis.