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Tumor necrosis factor receptor superfamily member 10B (TRAIL receptor 2) (TNFRSF10B (also known as DR5 or TRAIL-R2))

Target
TNFRSF10B (also known as DR5 or TRAIL-R2)
Molecular classification
Receptor, Tumor necrosis factor receptor superfamily (TNFRSF), Death receptor (contains an intracellular death domain)
01

Overview

Tumor necrosis factor receptor superfamily member 10B is a cell-surface death receptor of the TNF receptor superfamily that binds the ligand TRAIL (TNFSF10) to transmit apoptotic signals through its intracellular death domain. Upon activation, DR5 recruits the adaptor FADD and initiator caspases (caspase-8/10) to form the death-inducing signaling complex, leading to extrinsic apoptosis. It is therapeutically targeted in oncology with agonist antibodies and TRAIL or TRAIL-mimetic approaches.

Other names
Death receptor 5 (DR5)TRAIL receptor 2 (TRAIL-R2, TRAILR2)Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)CD262KILLERTRICK2ATRICKB
02

Mechanism of action

Agonist antibodies or TRAIL mimetics activate DR5, recruit FADD, and trigger caspase-8–mediated extrinsic apoptosis via DISC formation. TRAIL ligand binding to DR5 induces receptor trimerization and downstream apoptotic signaling.

03

Biological functions

Apoptosis induction via binding TRAIL (TNFSF10) and forming the death-inducing signaling complex (DISC)Signal transduction through adaptor FADD and initiator caspases (caspase-8, caspase-10)Immune response/tumor surveillance roles through TRAIL-mediated cytotoxic signaling
04

Disease associations

Cancer (therapeutic targeting; expression and regulation implicated in tumor cell apoptosis and resistance)Inflammation/immune pathways via TNF/TRAIL axis (context of TNF family signaling)
05

Safety considerations

On-target toxicity potential in normal tissues expressing DR5 (historically a consideration in clinical development of DR5 agonists)Variable efficacy due to tumor resistance mechanisms (e.g., low DR5 expression or defects in downstream apoptotic machinery)
06

Interacting drugs

Tigatuzumab (CS-1008)

1 more in the full profile.

07

Biomarkers

DR5 (TNFRSF10B) expression level as a potential predictor of response to TRAIL/DR5 agonists in tumorsTRAIL pathway components (e.g., FADD, caspase-8) as context biomarkers for apoptotic competence

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