Death Receptors and Stress Signaling Pathways in Therapeutic Intervention

Death receptors — members of the tumor necrosis factor receptor (TNFR) superfamily, including Fas (CD95), TNFR1, DR4, and DR5 — are critical mediators of programmed cell death and inflammatory signaling. When activated by their cognate ligands or by cellular stress, these receptors converge with intracellular stress signaling networks — including the unfolded protein response (UPR), oxidative stress pathways, DNA damage response, and mitochondrial dysfunction — to determine cell fate between survival, apoptosis, necroptosis, and autophagy.Dysregulation of death receptor signaling and stress-response cascades underpins a wide range of pathological conditions, including cancer, neurodegenerative diseases, cardiovascular disorders, and chronic inflammatory diseases. As such, these pathways have emerged as compelling targets for therapeutic intervention. TRAIL-based therapies, small-molecule sensitizers, kinase inhibitors, and combination strategies that exploit stress-induced vulnerabilities are among the most actively investigated approaches in experimental pharmacology and drug discovery.This Research Topic invites original research articles, reviews, and perspectives that explore the pharmacological modulation of death receptor pathways and stress signaling networks in the context of disease. We welcome contributions addressing, but not limited to, the following themes:Mechanistic studies of death receptor activation, signal transduction, and crosstalk with stress pathwaysDrug discovery efforts targeting TRAIL receptors, Fas/FasL, TNFR1, and downstream effectorsThe role of ER stress, oxidative stress, and the DNA damage response in sensitizing cells to death receptor-mediated apoptosisResistance mechanisms and strategies to overcome them in cancer and other diseasesNovel small molecules, biologics, and combination therapies exploiting death receptor and stress signaling vulnerabilitiesPreclinical models and translational approaches bridging experimental findings to therapeutic applications Topic editors: MIRZA BAIG, Yang Wang, Hanan S. Anbar, Annette Vivi Jacobsen Source: https://www.frontiersin.org/research-topics/82907/death-receptors-and-stress-signaling-pathways-in-therapeutic-intervention