SAMHD1 Research Digest — 2026-05-10¶
Generated by samhd1_monitor | Model: claude-sonnet-4-6
Summary: 37 papers evaluated | 12 high-relevance (≥7) | 20 medium (5–6) | 5 low (3–4) | 0 scored <3
🔴 High Relevance (Score 7–10)¶
Added to Zotero automatically
Mitochondrial 8-Oxoguanine DNA Glycosylase 1–Mitochondrial Permeability Transition Pore Axis Drives Mitochondrial DNA Escape and Accelerates Osteoarthritis Progression (from Orthopedics/osteoarthritis)
Shiqian Huang; Heting Yu; Weizhong Qi; Na Lin; Jianmao Chen — Research 2026
Score: 8/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, NLRP3, treatment-target, other
This paper directly demonstrates the OGG1-mPTP axis driving oxidized mtDNA escape → cytosolic mtDNA → cGAS-STING-NF-κB activation, mechanistically recapitulating the BLUE and PURPLE streams of the SAMHD1 A565T syndrome (VDAC1/mPTP-mediated mtDNA release and ox-mtDNA from impaired mitochondrial repair both feeding cGAS-STING), while cyclosporin A (mPTP inhibitor) and TH10785 (OGG1 activator) as intervention targets are directly translatable to therapeutic strategies for the dNTP pool expansion–driven mitochondrial pathology in SAMHD1 haploinsufficiency.
DOI: 10.34133/research.1235
Crosstalk between cGAS-STING and pyroptosis: From molecular mechanisms to therapeutic strategies. (from Pharmacology/drug discovery)
Hongquan Wang; Shuang Wu; Xuan Zhang; WeiHua Zheng; Zhiji Wang — International immunopharmacology 2026
Score: 8/10 | Pathways: cGAS-STING, NLRP3, VDAC1, treatment-target, AGS-spectrum, ME-CFS
This review directly addresses the cGAS-STING–pyroptosis (NLRP3/caspase-1) crosstalk that constitutes Loops A and B of the SAMHD1 haploinsufficiency mechanism, covers therapeutic targeting strategies including upstream nucleic acid sensing, core pathway modulation, and downstream effector control that map precisely onto proposed interventions (IMSB301, MCC950, VBIT-4), and frames these in autoimmune/interferonopathy and sterile inflammation contexts highly relevant to the family's convergent interferon-mitochondrial syndrome.
DOI: 10.1016/j.intimp.2026.116203
Emerging molecular mechanisms of cGAS-STING activation and regulation. (from Structural/molecular biology)
Yilin Liu; Kanglong Ma; Zhengfan Jiang — Molecular immunology 2026
Score: 8/10 | Pathways: cGAS-STING, JAK-STAT, AGS-spectrum, ME-CFS, treatment-target
This review directly covers the cGAS-STING pathway (Loop A in the disease mechanism), including structural activation by dsDNA, cGAMP synthesis and STING translocation, and novel regulatory mechanisms (sGAGs, biocondensates, manganese-independent activation) that are directly relevant to understanding how VDAC1 macropore-released cytosolic mtDNA fragments drive IRF3→IFN-I signaling in SAMHD1 haploinsufficiency, and identifies therapeutic targets applicable to this interferonopathy.
DOI: 10.1016/j.molimm.2026.02.008
The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor (from oncology)
Kui Zhao; Siyuan Cui; Na Wang; Qi Wei; Xuerui Wang — Journal of Translational Medicine 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, JAK-STAT, mTOR-lysosomal, treatment-target, IRF7-metabolic
This review directly addresses the cGAS-STING/mitochondrial metabolism axis—the BLUE stream of the disease mechanism—including mtDNA escape, STING spatiotemporal dynamics, and metabolic crosstalk that mirrors the interferonopathy-mitochondrial loop in SAMHD1 haploinsufficiency, while the treatment-target discussion of STING agonist optimization and metabolic modulation has translational relevance for the family's interferonopathy management.
DOI: 10.1186/s12967-026-07748-4
Mitochondrial DNA 6mA Methylation by METTL4 Drives Neuroinflammation via cGAS-STING Activation in Vascular Cognitive Impairment. (from Neurology/cerebrovascular)
Z. Gong; Ziyi Chen; Shuixian Sang; Lingfei Yang; H. Qin — Free radical biology & medicine 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, VDAC1, other
This paper directly demonstrates the mechanistic axis of oxidized mtDNA leakage activating cGAS-STING neuroinflammation—a core BLUE stream pathway in the SAMHD1 haploinsufficiency model—and introduces METTL4-mediated mtDNA epigenetic modification as an upstream driver of mtDNA escape, impaired ETC activity, and ROS production that converges on the same cGAS-STING-mediated inflammatory cascade relevant to the proband's interferon-mitochondrial syndrome.
DOI: 10.1016/j.freeradbiomed.2026.01.019
The roles of the mtDNA-cGAS-STING axis in tumor immunity: from immune activation to immune evasion (from Oncology/tumor immunology)
Na Huang; Zheng Liu; Haibo Lei; Xiang Liu — Frontiers in Immunology 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, JAK-STAT, IRF7-metabolic, BIK-cancer, treatment-target
This review directly covers the mtDNA-cGAS-STING-IRF3-IFN-I axis (the BLUE stream of the disease mechanism) in comprehensive detail, including mtDNA leakage triggers, cGAMP synthesis, downstream IFN-I induction, and therapeutic targeting strategies (STING modulators, nano-delivery), all of which are core to SAMHD1 haploinsufficiency pathophysiology, though the tumor immunity framing is tangential to the primary interferonopathy/ME-CFS phenotype.
DOI: 10.3389/fimmu.2025.1739559
mtDNA leakage promotes neuron-glia crosstalk to induce epilepsy by cGAS-STING-driven neuroinflammation and serine metabolic reprogramming. (from Neurology/Epileptology)
Jie Jiang; Meiling Zuo; Kehan Zhao; Zhihao Ling; Zhida Wu — Proceedings of the National Academy of Sciences of the United States of America 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, NLRP3, treatment-target, other
This paper directly demonstrates the mtDNA leakage → cGAS-STING → neuroinflammation axis in a CNS context, with pharmacologic STING inhibition (H-151) suppressing disease, providing mechanistic and therapeutic validation for the BLUE stream of the SAMHD1 haploinsufficiency model, while also introducing a novel metabolic reprogramming downstream consequence (D-serine/NMDA excitotoxicity) that could explain neurological phenotypes (ASD/ADHD, possible seizure susceptibility) in the family.
DOI: 10.1073/pnas.2522313123
Protective and pathogenic: The Janus-faced role of cGAS-STING in the brain. (from Neurology/cerebrovascular)
C. Corona; Christina Kanzlemar; A. Hussaini; R. Ratan — Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2026
Score: 7/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, ME-CFS, AGS-spectrum, mTOR-lysosomal
This paper directly characterizes cGAS-STING/IFN-I signaling as enforcing a 'metabolic austerity program' that suppresses synaptic plasticity when chronically activated—a mechanism highly relevant to the SAMHD1 A565T family's neurocognitive phenotypes (AuDHD, cognitive fatigue, ME/CFS) driven by constitutive BLUE-stream cGAS-STING activation, and the distinction between transient vs. sustained IFN-I activation maps directly onto the haploinsufficiency's tonic low-grade interferonopathy.
DOI: 10.1177/0271678X261427904
CircZBTB44-Encoded Peptide ZBTB44-342aa Alleviates Aortic Valve Calcification Via cGAS-STING Inhibition. (from Cardiology / valvular disease)
Dongtu Hu; Yingwen Lin; Hai-Bo Huang; G. Xian; Yubing Chen — Circulation research 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target
This paper directly demonstrates that mtDNA cytosolic release activates cGAS-STING to drive pathological osteogenic differentiation, and identifies STING inhibition (H-151) as therapeutic—mechanistically parallel to the BLUE stream (VDAC1 → mtDNA escape → cGAS → STING → IRF3 → IFN-I) central to the SAMHD1 A565T syndrome, with the added novel mechanistic detail that IGF2BP3 suppresses mitochondrial damage and mtDNA release upstream of cGAS-STING.
DOI: 10.1161/CIRCRESAHA.125.326771
Targeting the cGAS-STING-TBK1 pathway in cancer therapy. (from Oncology)
Leyao Jiang; Y. Zhong; Zilong Zhang; Qicheng Yang; Shengting Sun — Future medicinal chemistry 2026
Score: 7/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, treatment-target, BIK-cancer
This review directly covers the cGAS-STING-TBK1 axis—the BLUE stream core pathway in the disease mechanism—including its dual role in cancer (relevant to SAMHD1 tumor suppressor function) and targeted therapeutic agents such as STING agonists/antagonists and TBK1 inhibitors that represent treatment candidates for the interferonopathy component of the syndrome.
DOI: 10.1080/17568919.2026.2628553
Abstract 389: GSDMB drives cGAS-STING-mediated immune evasion in HER2-amplified colorectal cancer. (from Oncology (colorectal cancer / HER2-amplified CRC))
Junyong Weng; Tianchen Xiong; Xinxiang Li; Ajay Goel — Cancer Research 2026
Score: 7/10 | Pathways: cGAS-STING, VDAC1, JAK-STAT, BIK-cancer, other
GSDMB-driven mitochondrial membrane pore formation causing chronic low-level mtDNA leakage into the cytosol activating cGAS-STING with downstream IFNα response directly mirrors the BLUE pathway (VDAC1 macropore → cytosolic mtDNA → cGAS → STING → IRF3 → IFN-I) central to SAMHD1 haploinsufficiency, and demonstrates a novel pore-forming mechanism linking mitochondrial integrity loss to chronic interferonopathy in a cancer context relevant to the family's BIK-cancer axis.
DOI: 10.1158/1538-7445.am2026-389
Integrative transcriptomic profiling links telomere dysfunction to cGAS–STING activation in heart failure signatures in mice and humans (from Cardiology)
M. Brandt; S. Khraisat; Q. Luo; M. Mayerle; U. Raaz — Cardiovascular Research 2026
Score: 7/10 | Pathways: cGAS-STING, POLG-mtDNA, JAK-STAT, ISG15-mitophagy, clinical-phenotype
This paper provides first direct evidence that telomere shortening activates cGAS-STING → type I interferon signaling in cardiomyocytes via a telomere-p53-mitochondria axis, directly paralleling the BLUE and RED streams of the SAMHD1 haploinsufficiency mechanism (cytosolic DNA → cGAS → STING → IRF3 → IFN-I → JAK-STAT), and contextualizes interferon-driven cardiac dysfunction as a clinically relevant endpoint relevant to the family's interferonopathy cardiovascular risk.
DOI: 10.1093/cvr/cvag013
🟡 Medium Relevance (Score 5–6)¶
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Simultaneous activation of apoptosis and cGAS-STING pathway with a mitochondria-targeted dehydrocholic acid compound for enhanced hepatocellular carcinoma chemoimmunotherapy. (from Oncology/pharmacology)
Fuwei Li; Sizhe Zhu; Xinyu Sun; Guangxing Geng; Jiawen Zhao — Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, BIK-cancer, treatment-target
This paper directly demonstrates the mechanistic link between mitochondrial permeability transition pore opening, cytosolic mtDNA release, and cGAS-STING activation in hepatocellular carcinoma — recapitulating the BLUE stream of the SAMHD1 haploinsufficiency mechanism (VDAC1 macropore → cytosolic mtDNA → cGAS → STING → IRF3 → IFN-I) and is further relevant given the family's hepatic phenotype (hepatic steatosis, cholecystectomy clustering) and SAMHD1's tumor suppressor role, though the context is therapeutic oncology rather than constitutive interferonopathy.
DOI: 10.1016/j.biopha.2026.119044
Spleen Tyrosine Kinase (SYK) is Necessary for cGAS‐STING Signaling in Müller Glia and Visual Function Deficits in Diabetic Mice (from Ophthalmology/Retinal Neuroscience)
Esma I. Yerlikaya; S. Sunilkumar; Sandeep M. Subrahmanian; Allyson L. Toro; Clay — Glia 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, NLRP3, JAK-STAT, other
This paper directly demonstrates the mechanistic link between mitochondrial membrane permeability → cytosolic mtDNA → cGAS-STING → NF-κB → IL-1β/CCL2 (MCP-1) activation, which maps precisely onto the BLUE stream of the SAMHD1 haploinsufficiency model, and introduces SYK as a novel required intermediary in cGAS-STING signaling with potential therapeutic targeting relevance, though the disease context is diabetic retinopathy rather than SAMHD1 dysfunction.
DOI: 10.1002/glia.70155
Pharmacological activation of cGAS-STING pathway to reverse cancer drug resistance. (from oncology)
Yumin Wang; Yan Wang; Q. Gao; Yonglin Zhu; Yulin Li — Pharmacology & therapeutics 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, treatment-target, BIK-cancer, other
This review directly covers the cGAS-STING pathway—a core Loop A mechanism in SAMHD1 haploinsufficiency—and describes how epigenetic, post-translational, and metabolic suppression of cGAS-STING promotes drug resistance, which is directly relevant to understanding modulators of this pathway and potential therapeutic targets, though the oncology framing (reactivating a suppressed pathway) is the mirror-image of the disease context here (a constitutively hyperactive cGAS-STING from SAMHD1 loss-of-function), making it an adjacent rather than direct mechanistic match.
DOI: 10.1016/j.pharmthera.2026.108991
Mangiferin inhibits cGAS-STING pathway-related inflammation via Nrf2 activation to protect against sepsis-induced heart injury (from Cardiology/Traditional Chinese Medicine)
Junna Song; Meng Wang; Qian Li; Wanting Zhao; Xiangming Chen — Chinese Medicine 2026
Score: 6/10 | Pathways: cGAS-STING, VDAC1, POLG-mtDNA, treatment-target, other
This paper directly addresses mtDNA release, mitochondrial membrane integrity (mPTP/VDAC-adjacent), and cGAS-STING-driven cardiac inflammation with a natural compound (mangiferin/Nrf2) that suppresses the same cGAS-STING axis central to the SAMHD1 interferonopathy mechanism, offering a potentially translatable treatment angle for the interferon-mitochondrial syndrome, though the context is LPS-sepsis rather than SAMHD1 haploinsufficiency.
DOI: 10.1186/s13020-026-01329-9
Selenium regulates pyroptosis through the ROS-mtDNA-cGAS-STING axis to alleviate trimethyltin chloride-induced inflammation in chicken kidneys. (from Veterinary toxicology / comparative physiology)
Huiling Zheng; Xinyu Huo; Wenwen Zhang; Shuang Lou; Mingyue Li — Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, treatment-target, other
This paper directly demonstrates the ROS→mitochondrial dysfunction→mtDNA leakage→cGAS-STING→NLRP3/pyroptosis cascade (BLUE and PURPLE streams) and validates selenium as a therapeutic modulator of this axis, providing mechanistic and pharmacological context highly relevant to the SAMHD1 interferonopathy model where the same mtDNA-cGAS-STING-NLRP3 convergence is central, though the disease context (organotin nephrotoxicity in chickens) is entirely distinct from SAMHD1 haploinsufficiency.
DOI: 10.1016/j.cbpc.2026.110452
The Role of the cGAS-STING Pathway in Central Nervous System Diseases (from Neurology)
Xiangning He; Xunlu Yin; Qian Chen; Haoyuan Gao; Fangfang Zhao — CNS & Neurological Disorders - Drug Targets 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, treatment-target, ME-CFS
This review directly covers the cGAS-STING pathway (BLUE stream) in CNS disease contexts including neuroinflammation, autophagy, and apoptosis, with therapeutic inhibitors discussed (C-176, H-151, RU.521), which are directly relevant to the SAMHD1/VDAC1/cGAS/STING axis driving neurological manifestations (AuDHD, ME/CFS, potential dystonia) in this family, though it lacks SAMHD1-specific or mitochondrial dNTP-pool mechanistic content.
DOI: 10.2174/0118715273428657260309045542
Lipids Meet Immunity: Metabolic Control of cGAS-STING (from Lipidology/Immunometabolism)
C. Mah; Xuan Yuan Aw; Ngee Kiat Chua — Lipidology 2026
Score: 6/10 | Pathways: cGAS-STING, IRF7-metabolic, mTOR-lysosomal, other
This review directly addresses metabolic regulation of the cGAS-STING pathway—the BLUE stream core mechanism—through lipid biology, covering how lipid metabolism (including membrane compartmentalization, cholesterol, fatty acids) modulates STING activation and signaling dynamics, which is directly relevant to the VDAC1-mtDNA-cGAS-STING axis in this disease and adjacent to the hepatic steatosis and metabolic reprogramming phenotypes observed in the family.
DOI: 10.3390/lipidology3010010
The roles of cGAS-STING pathway in cancer (from Oncology)
Jijun Sun; Ruijuan Wang; Jue Wang; Lele Zhang — Oncology and Translational Medicine 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, IRF7-metabolic, BIK-cancer, treatment-target, clinical-phenotype
This review directly covers the cGAS-STING pathway (BLUE stream core mechanism) with extensions into pyroptosis/NLRP3 crosstalk and cancer contexts relevant to the family's tumor phenotypes (multiple myeloma, endometrial, prostate, duodenal cancers), and discusses STING agonists/inhibitors as therapeutic targets, but does not address SAMHD1, mitochondrial mechanisms, ISG15-mitophagy, or VDAC1 specifically.
DOI: 10.1097/ot9.0000000000000136
Resveratrol Mitigates Age-Associated Cognitive Decline via Inhibition of cGAS-STING-Mediated Microglial Senescence (from Neuroscience/gerontology)
Xinxin Duan; Jiahui Cheng; Jiayao Wang; Wen Chen; Zhi Ruan — Cells 2026
Score: 6/10 | Pathways: cGAS-STING, NLRP3, JAK-STAT, ME-CFS, treatment-target
This paper directly investigates cGAS-STING pathway suppression as a therapeutic target for neuroinflammation and cognitive decline, with downstream IL-1β and CXCL-10 reduction highly relevant to the BLUE and RED streams of the SAMHD1 interferonopathy mechanism, and resveratrol's mechanism (potentially via SIRT1/PGC-1α activation and cGAS inhibition) offers a plausible treatment-target insight for managing chronic IFN-I signaling in SAMHD1 haploinsufficiency, though the context is aging/galactose-induced senescence rather than SAMHD1 mutation.
DOI: 10.3390/cells15060523
TRIM69 potentiates the cGAS-STING signalling pathway by promoting STING ubiquitination. (from Virology/antiviral innate immunity)
Shixin Chen; Li Yi; Mengzhou Xue; Chunfu Zheng — Cellular signalling 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, treatment-target
TRIM69-mediated K63-ubiquitination of STING enhances cGAS-STING-IFN-I signaling, directly relevant to the BLUE stream where SAMHD1/VDAC1 loss drives cytosolic mtDNA→cGAS→STING→IRF3→IFN-I, as a novel positive regulator that could amplify the already dysregulated interferonopathy in this family; however, no direct SAMHD1, mitochondrial, or clinical phenotype connection is demonstrated.
DOI: 10.1016/j.cellsig.2026.112495
cGAS-STING signaling: a therapeutic target in inflammatory bowel disease and related colorectal cancer (from Gastroenterology/Oncology)
Xi Chen; Xiaohua Tang; Sixuan Chen; Yang Ye; Fei Mao — Frontiers in Immunology 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, NLRP3, treatment-target, IRF7-metabolic, clinical-phenotype
This review directly covers the cGAS-STING pathway (a core BLUE stream component in the disease mechanism) and its bidirectional regulation including IFN-I and proinflammatory cytokine production, with therapeutic targeting implications relevant to interferonopathy management, though it focuses on intestinal disease contexts rather than SAMHD1 haploinsufficiency or mitochondrial pathology specifically.
DOI: 10.3389/fimmu.2025.1709908
Targeting the cGAS-STING pathway in ophthalmology: from innate immunity to therapeutic innovation. (from Ophthalmology)
Dan Yan; Weijie Ouyang; Kuanshu Li; Xuguang Sun — Experimental eye research 2026
Score: 6/10 | Pathways: cGAS-STING, JAK-STAT, mTOR-lysosomal, AGS-spectrum, treatment-target, clinical-phenotype
This review directly covers the cGAS-STING pathway (BLUE stream core mechanism) with therapeutic targeting implications, and notably flags glaucoma as a cGAS-STING-driven ocular disease—glaucoma appears in the tracked family phenotype list—providing a mechanistic bridge between the interferonopathy and a documented familial clinical feature, while the autophagy/senescence/cell-death interactions also touch ISG15-mitophagy and mTOR-lysosomal axes.
DOI: 10.1016/j.exer.2026.110978
Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications (from Oncology/Cancer Immunotherapy)
Lusheng Wang; Sudi Zhu; Zhixian Ding; Jie Hong; Lijie Zheng — Journal of Translational Medicine 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, treatment-target
This paper covers cGAS-STING signaling comprehensively in the tumor immunotherapy context, including cell-type-specific activation dynamics, chronic vs. acute signaling consequences, and therapeutic modulation strategies that are mechanistically relevant to the SAMHD1 haploinsufficiency disease model (where dysregulated cGAS-STING via VDAC1 macropore/mtDNA escape drives Loop A), but the focus is entirely oncologic/immunotherapeutic rather than interferonopathy or SAMHD1-related disease.
DOI: 10.1186/s12967-025-07645-2
Cutaneous human papillomavirus E6 impairs the cGAS-STING pathway (from Virology/Dermatology-oncology)
Grant Brooke; D. Dacus; Rose Pollina; Katsura Asano; N. Wallace — mSphere 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, other
This paper directly characterizes cGAS-STING pathway suppression by a viral protein (β-HPV E6), which is mechanistically relevant to the BLUE stream of the disease model where cytosolic dsDNA activates cGAS→STING→IRF3→IFN-I, but the context is viral immune evasion in skin cancer rather than SAMHD1 haploinsufficiency, making it an indirect connection that illuminates cGAS-STING modulation without direct mechanistic import to the family phenotype.
DOI: 10.1128/msphere.00859-25
Calibrating the RT-cGAS-STING axis to drive cold-to-hot tumor transformation: mechanistic foundations and translational strategies for combination with immunotherapy (from Radiation oncology / tumor immunology)
Yi-fan Kang; Jin-ming Chen; Bai Xu; Jun-Nv Xu; Qixian Qin — Molecular Cancer 2026
Score: 5/10 | Pathways: cGAS-STING, IRF7-metabolic, JAK-STAT, treatment-target, other
This review covers the cGAS-STING-IFN-I axis in depth (Loop A of the disease mechanism) and discusses regulatory nodes like TREX1 and apoptotic caspases, with translational treatment implications, but is framed entirely within radiotherapy-oncology and does not address SAMHD1, mitochondrial dNTP pools, VDAC1, ISG15-mitophagy, or the interferonopathy-fatigue spectrum relevant to this family.
DOI: 10.1186/s12943-026-02636-3
cGAS-STING Signaling Pathway in Urogenital Oncology: Regulation, Resistance, and Routes to Response. (from Oncology/Urology)
Chen Gong; Senmao Li; Ying Huang; Enxiu Luo; Zhiyong Tan — Critical reviews in oncology/hematology 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, BIK-cancer, treatment-target
This review covers cGAS-STING signaling in urogenital oncology with mechanistic detail on phosphorylation/ubiquitination regulation, STING agonists, and interferon competence circuits that are directly relevant to the BLUE stream of the SAMHD1 mechanism, and touches on prostate cancer (BIK-axis family phenotype), but remains oncology-focused and does not address SAMHD1, mitochondrial dysfunction, ISG15-mitophagy, or the interferonopathy/ME-CFS clinical context.
DOI: 10.1016/j.critrevonc.2026.105222
Loss of XRCC1 promotes cGAS/STING mediated innate immune signaling in gastric cancer (from Oncology/gastroenterology)
Aashirwad Shahi; Shengyuan Zhao; Julia A. Goewey Ruiz; Dawit Kidane — Molecular Medicine 2026
Score: 5/10 | Pathways: cGAS-STING, other
This paper mechanistically demonstrates that nuclear DNA repair deficiency (XRCC1 loss) triggers cytosolic DNA accumulation and cGAS/STING-mediated type I interferon signaling, which is directly analogous to the BLUE stream in the SAMHD1 A565T model where dNTP pool imbalance and VDAC1 dysfunction release mtDNA to activate cGAS/STING, but the specific molecular actors (XRCC1 vs. SAMHD1, nuclear SSBs vs. cytosolic dNTP/mtDNA) and clinical context (gastric cancer vs. interferonopathy) are sufficiently distinct to limit direct translational relevance.
DOI: 10.1186/s10020-026-01429-0
Abstract A003: Chronic cGAS–STING activation reprograms glioblastoma-associated macrophages toward immunosuppression in hypoxic tumor niches (from Neuro-oncology)
Sebastian Ouyang; Virginia Wertman; Michael Brown; Matthew S. Waitkus; Justin T. — Cancer Research 2026
Score: 5/10 | Pathways: cGAS-STING, JAK-STAT, IRF7-metabolic, other
This paper directly investigates cGAS-STING signaling and demonstrates that chronic/sustained STING activation leads to loss of interferon signaling and metabolic reprogramming, which is mechanistically relevant to understanding how the constitutive low-level cGAS-STING activation hypothesized in SAMHD1 haploinsufficiency might paradoxically shift toward immunosuppression over time, but the context is glioblastoma tumor immunology rather than interferonopathy or mitochondrial disease.
DOI: 10.1158/1538-7445.brain26-a003
Venezuelan Equine Encephalitis Virus Antagonizes the cGAS-STING Pathway (from Virology/Infectious Disease)
Brittany N. Heath; Maryna Akhrymuk; Abdullahi Temitope Jamiu; I. Akhrymuk; A. Pi — Cells 2026
Score: 5/10 | Pathways: cGAS-STING, ISG15-mitophagy, JAK-STAT, ME-CFS, other
This paper directly investigates cGAS-STING pathway modulation by an RNA virus (VEEV), demonstrating viral antagonism of STING phosphorylation and noncanonical ISG induction, which is mechanistically relevant to the BLUE and RED streams of the SAMHD1 syndrome (where dysregulated cGAS-STING drives IFN-I → ISGylation → mitophagy block), and the post-viral ME/CFS trigger context (adenovirus/SARS-CoV-2 in proband), but the connection is indirect as VEEV is not a documented trigger and no SAMHD1 or haploinsufficiency data are presented.
DOI: 10.3390/cells15040327
Pueraria flavones attenuate DSS-induced colitis by regulating the microbiota-bile acid-FXR/TGR5 axis and suppressing mtDNA-cGAS-STING signaling (from Gastroenterology/Pharmacognosy)
Liheng Kang; Chunsheng Feng; Ziyi Tang; Wanping Gu; Ying Wang — iScience 2026
Score: 5/10 | Pathways: cGAS-STING, POLG-mtDNA, other
This paper directly demonstrates the mtDNA-release → cGAS-STING axis as a colitis driver and its suppression by a therapeutic agent, which is mechanistically relevant to the BLUE stream (VDAC1/mtDNA/cGAS/STING/IFN-I) of the SAMHD1 syndrome, but the colitis context, plant flavone intervention, microbiota-bile acid framing, and absence of any interferonopathy/SAMHD1 connection make it only an indirect mechanistic parallel rather than a directly actionable finding.
DOI: 10.1016/j.isci.2026.115275
🟢 Low Relevance (Score 3–4)¶
Potential specialty bridges — skim titles
C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer (from Oncology/Radiation Oncology)
Trang Thao Quoc Pham; Pei-Ju Lee; Nguyen Quoc Khanh Le — iScience 2026
Score: 4/10 | Pathways: cGAS-STING, other
The paper discusses cGAS/STING in the context of colorectal cancer radiosensitivity and complement C5a/C5aR1 suppression of STING-driven IFN-beta, which touches the cGAS-STING pathway central to the BLUE stream, but the oncologic and radiotherapy framing is tangential to the SAMHD1 haploinsufficiency interferonopathy mechanism and adds no direct mechanistic or clinical insight relevant to the family phenotype.
DOI: 10.1016/j.isci.2026.115009
Targeting redox metabolism and low-dose radiotherapy synergistically activate cGAS-STING pathway to improve NK cell therapy efficacy in hepatocellular carcinoma (from Oncology/Nanomedicine)
Bo Liu; Wenjia Kong; Xijie Zhang; Bo Ren; Yusheng Cheng — Journal of Nanobiotechnology 2026
Score: 4/10 | Pathways: cGAS-STING, treatment-target, other
This paper involves cGAS-STING pathway activation as a mechanism but in the context of HCC tumor immunotherapy via redox manipulation and NK cell recruitment, with no connection to SAMHD1 haploinsufficiency, interferonopathy, mitochondrial dNTP pools, or any family phenotype; the cGAS-STING relevance is mechanistically superficial relative to the disease profile.
DOI: 10.1186/s12951-026-04171-1
EEPD1 Inhibition Unleashes Antitumor Immunity in Colorectal Cancer by Activating the cGAS‐STING Pathway (from oncology)
L. Huo; Chong Wu; Xiaobo Li; Caina Ma; Jiaming Huang — Advanced Science 2026
Score: 4/10 | Pathways: cGAS-STING, other
This paper activates cGAS-STING via cytosolic DNA from genomic instability (HR deficiency), which shares the cGAS-STING-type I interferon axis central to the SAMHD1 mechanism, but the driver is nuclear DNA damage rather than dNTP pool dysregulation or mtDNA escape, and the clinical context (CRC immunotherapy sensitization) is only tangentially related to the SAMHD1 interferonopathy syndrome.
DOI: 10.1002/advs.202522826
Biomimetic Iridium‐Based Photothermal Nanozyme to Trigger Ferroptosis and Pyroptosis and Activate the cGAS‐STING Pathway for Improved Tumor Immunotherapy (from Oncology/Nanomedicine)
Lijun Ding; Zhongxiong Fan; Guoyu Xia; Fukai Zhu; N. Yang — Advanced Science 2026
Score: 4/10 | Pathways: cGAS-STING, NLRP3, POLG-mtDNA, other
This oncology nanomedicine paper deliberately induces mtDNA oxidative damage and cGAS-STING activation as a therapeutic mechanism for tumor immunotherapy, touching on core pathways (cGAS-STING, pyroptosis/NLRP3, mtDNA release) relevant to the SAMHD1 disease model, but entirely in an artificial photothermal/ROS cancer context with no connection to SAMHD1 haploinsufficiency, interferonopathy, or the family phenotype.
DOI: 10.1002/advs.202519186
Leveraging Naturally Assembled Tumor Extracellular Vesicles as Self-Adjuvanting Nanovaccines to Potentiate Cancer Immunotherapy via cGAS/STING Activation. (from Oncology/nanomedicine)
Jianing Gong; K. Liang; Yinzhe Sun; Laozhi Xie; Yukun Huang — ACS nano 2026
Score: 3/10 | Pathways: cGAS-STING, other
This paper exploits cGAS/STING activation as a cancer immunotherapy tool using engineered extracellular vesicles, which is mechanistically adjacent to the BLUE stream of the disease profile but is focused on therapeutic oncology engineering rather than providing any mechanistic insight into SAMHD1 haploinsufficiency, interferonopathy, or the pathological consequences of dysregulated cGAS-STING signaling relevant to the family phenotype.
DOI: 10.1021/acsnano.5c15637
Pathway Coverage This Week¶
cGAS-STING: 37 paperstreatment-target: 22 papersother: 20 papersJAK-STAT: 20 papersPOLG-mtDNA: 12 papersIRF7-metabolic: 12 papersVDAC1: 11 papersNLRP3: 9 papersBIK-cancer: 7 papersME-CFS: 6 papersAGS-spectrum: 4 papersmTOR-lysosomal: 4 papersclinical-phenotype: 4 papersISG15-mitophagy: 2 papers