ArticleCancer discovery2024
Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 92 citations in OpenAlex.
- Elevated CHAF1A Suppresses Type I Interferon Production and Causes Immunotherapy Resistance in Esophageal Squamous Cell Carcinoma.Cancer immunology research · 2026Article
- GSLR Drives Lung Adenocarcinoma as a Critical Regulator of Energy Homeostasis Through Creatine Kinase B Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tumour-associated dsRNA accumulation and innate immune activation: mechanistic basis and therapeutic strategies.EBioMedicine · 2026Review
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Review
- Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-stranded RNA triggered antitumor immunity.Nature communications · 2026Article
- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- Dihydroartemisinin inhibits mutant KRAS to potentiate regorafenib plus anti-PD-1 in KRAS-mutant colorectal cancer liver metastases.Cell death & disease · 2026Article
- Tumor cell intrinsic dsRNA innate immune response triggered by PARP inhibitor is compromised in BRCA1-deficient breast cancer by repressing IRF3.Protein & cell · 2026Article
- KDM4B/DHX9 promotes chemoresistance in small-cell lung cancer through the MYCN-driven signaling pathway.Oncogene · 2026Article
- DHX9 transcriptional upregulation and lactylation at K1024 fuels a glycolysis-histone lactylation loop in osteosarcoma.Journal of translational medicine · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- DHX37 protein and mRNA expression patterns in breast and ovarian cancer and their prognostic implications.Histochemistry and cell biology · 2026Article
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- Control of retrotransposon-driven activation of the interferon response by the double-stranded RNA binding protein DGCR8.Nucleic acids research · 2026Article
- CD38 degrades MAVS through mitophagy to inhibit type I interferon secretion in nasopharyngeal carcinoma cells and impairs CD8Nature communications · 2026Article
- Viral mimicry acts as a tumor suppressor in colitis.Nature communications · 2026Article
- Targeting WEE1 in ARID1A/TP53 Concurrent Mutant Colorectal Cancer by Exploiting R-Loop Accumulation and DNA Repair Deficiencies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PCBP1 binding to single-stranded poly-cytosine motifs enhances cGAS sensing and impairs breast cancer development.Communications biology · 2026Article
- GPSAdb 2.0: an expanded atlas of gene-perturbation transcriptomes with enhanced tools for regulatory gene discovery.Nucleic acids research · 2026Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
Activating innate immunity in cancer cells through cytoplasmic nucleic acid sensing pathways, a phenomenon known as "viral mimicry," has emerged as an effective strategy to convert immunologically "cold" tumors into "hot." Through a curated CRISPR-based screen of RNA helicases, we identified DExD/H-box helicase 9 (DHX9) as a potent repressor of double-stranded RNA (dsRNA) in small cell lung cancers (SCLC). Depletion of DHX9 induced accumulation of cytoplasmic dsRNA and triggered tumor-intrinsic innate immunity. Intriguingly, ablating DHX9 also induced aberrant accumulation of R-loops, which resulted in an increase of DNA damage-derived cytoplasmic DNA and replication stress in SCLCs. In vivo, DHX9 deletion promoted a decrease in tumor growth while inducing a more immunogenic tumor microenvironment, invigorating responsiveness to immune-checkpoint blockade. These findings suggest that DHX9 is a crucial repressor of tumor-intrinsic innate immunity and replication stress, representing a promising target for SCLC and other "cold" tumors in which genomic instability contributes to pathology. SIGNIFICANCE: One promising strategy to trigger an immune response within tumors and enhance immunotherapy efficacy is by inducing endogenous "virus-mimetic" nucleic acid accumulation. Here, we identify DHX9 as a viral-mimicry-inducing factor involved in the suppression of double-stranded RNAs and R-loops and propose DHX9 as a novel target to enhance antitumor immunity. See related commentary by Chiappinelli, p. 389. This article is featured in Selected Articles from This Issue, p. 384.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.