Stress-Responsive Gene Networks as Drug Targets

Recent advances in molecular pharmacology, systems biology, genomics, and transcriptomics have transformed our understanding of disease pathogenesis and drug target identification. We now recognize human diseases as complex, interconnected conditions driven by dysregulated cellular signalling, immune responses, environmental stressors, and genetic regulation. Cellular stress responses — including oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, hypoxia, metabolic imbalance, and inflammatory signalling — drive disease initiation and progression, and represent a rich landscape of pharmacologically actionable targets. Stress-responsive gene networks, regulated by NF-κB, Nrf2, JAK/STAT, MAPK, HIF-1α, and inflammasomes, shape immunity, inflammation, cell survival, and tissue integrity. Disrupting or modulating these adaptive molecular networks contributes to cancer, autoimmune disorders, infectious diseases, metabolic syndromes, and neurodegenerative conditions. Understanding these mechanisms reveals opportunities for biomarker discovery, drug target validation, and the development of targeted, disease-modifying therapeutics.This Research Topic will create an interdisciplinary platform integrating experimental pharmacology, molecular pharmacology, systems biology, neuroimmunology, and translational medicine, with a focus on how stress-responsive gene networks can be exploited for drug discovery and development. Manuscripts focusing on how cellular stress signalling pathways control immune responses, inflammation, metabolic adaptation, tissue injury, and disease progression are welcome, particularly where findings carry pharmacological relevance or therapeutic implications. This topic also includes manuscripts that explore transcriptional and post-transcriptional regulation, neuroinflammation, epigenetic changes, transcriptomic profiling, stress-driven cell reprogramming, therapeutic resistance, and targeted interventions, as well as new biomarkers and therapeutic strategies. We encourage studies that apply multi-omics, single-cell sequencing, and computational approaches — including machine learning-based target prediction, AI-assisted compound screening, and network pharmacology modelling — to identify and validate stress-responsive drug targets. We also welcome translational work on small molecules, biologics, gene therapies, and precision medicine strategies directed at stress signalling pathways. This collection links molecular discovery to therapeutic development to accelerate new treatments for immune, inflammatory, metabolic, and neurological diseases.We welcome submissions — Original Research, Reviews, Mini Reviews, and Perspectives — on stress-responsive gene networks in disease and drug discovery. Authors benefit from increased visibility within a multidisciplinary research community and opportunities to highlight key advances in disease mechanisms, drug target identification, and therapeutic strategies. We consider research on immunological, neurological, metabolic, infectious, autoimmune, and cancer disorders. Authors should focus on mechanistic, pharmacologically relevant, and translational research that advances the understanding and therapeutic exploitation of stress-responsive molecular pathways in human disease. Topic editors: Himanshu Narayan Singh, Vishnu Swarup Source: https://www.frontiersin.org/research-topics/81842/stress-responsive-gene-networks-as-drug-targets