Tumor necrosis factor receptor superfamily member 10B (Death receptor 5) (DR5)

Tumor necrosis factor receptor superfamily member 10B, commonly known as Death Receptor 5 (DR5), is a cell surface receptor that plays a critical role in the extrinsic apoptosis pathway. Upon binding to its ligand, Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), DR5 clusters and recruits the adapter protein FADD and pro-caspase-8 to form the death-inducing signaling complex (DISC). This activation triggers a proteolytic cascade involving downstream caspases, ultimately leading to programmed cell death. DR5 is highly attractive as a therapeutic target because it is frequently overexpressed in various malignancies—including colorectal, lung, and pancreatic cancers—while its activation appears to selectively induce apoptosis in tumor cells over normal cells. Clinical development has focused on recombinant TRAIL variants and agonistic monoclonal antibodies designed to mimic ligand binding. Despite early challenges with drug potency and tumor resistance, next-generation multivalent agonists and combination therapies targeting DR5 continue to be investigated for their potential to overcome apoptotic evasion in refractory tumors.

Other names

TNFRSF10BTRAIL receptor 2TRAIL-R2CD262KILLERTRICK2ZTNFR9

Agonism of the DR5 receptor to induce the formation of the death-inducing signaling complex (DISC), leading to caspase-8 activation and subsequent apoptosis in cancer cells.