ArticleCancer medicine2023
Immunogenicity of small-cell lung cancer associates with STING pathway activation and is enhanced by ATR and TOP1 inhibition.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Ferroptosis as a Translational Axis in Small Cell Lung Cancer: A Systematic Review of Redox Pathways and Precision Oncology Prospects.Oncology research · 2026Pooled it
- STING expression in pituitary neuroendocrine tumour immune microenvironments.Endocrine-related cancer · 2026Article
- cGAS-STING pathway in lung cancer and emerging therapeutic approaches.Drug discovery today · 2026Review
- The role of cGAS-STING signaling pathway in ferroptosis.Journal of advanced research · 2025Review
- Unlocking the therapeutic potential of the STING signaling pathway in anti-tumor treatment.Clinical and experimental medicine · 2025Review
- Shared Genomic Features Between Lung Adenocarcinoma and Type 2 Diabetes: A Bioinformatics Study.Biology · 2025Article
- Stimulation of cGAS-STING pathway as a challenge in the treatment of small cell lung cancer: a feasible strategy?British journal of cancer · 2024Review
- ATR inhibition activates cancer cell cGAS/STING-interferon signaling and promotes antitumor immunity in small-cell lung cancer.Science advances · 2024Article
- GCN2 is a determinant of the response to WEE1 kinase inhibition in small-cell lung cancer.Cell reports · 2024Article
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- Small cells - big issues: biological implications and preclinical advancements in small cell lung cancer.Molecular cancer · 2024Review
- Understanding Cancer's Defense against Topoisomerase-Active Drugs: A Comprehensive Review.Cancers · 2024Review
- A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.Nature communications · 2024Article
- Does subtyping of high-grade pulmonary neuroendocrine carcinomas have an impact on therapy selection?Translational lung cancer research · 2023Article
- Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- Could Inhibiting the DNA Damage Repair Checkpoint Rescue Immune-Checkpoint-Inhibitor-Resistant Endometrial Cancer?Journal of clinical medicine · 2023Review
- Immunogenicity of small-cell lung cancer associates with STING pathway activation and is enhanced by ATR and TOP1 inhibition.Cancer medicine · 2023Article
- cGAS-STING Pathway as the Target of Immunotherapy for Lung Cancer.Current cancer drug targets · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe activation of STING (stimulator of interferon genes) pathway enhances antitumor immunity in small-cell lung cancer (SCLC), while the DNA damage induced by non-cGAMP-based agonists is a potent inducer of STING activity. Here, we investigate the intrinsic expression of STING in cancer cells and evaluate the value of the combination of ATR and TOP1 inhibitors in enhancing antitumor immunity.
methodsSTING expression was assessed at mRNA and protein levels in SCLC and normal lung tissues. Transcriptomic subsets of SCLC were identified based on STING-related genes. Distinct mutation and immunogenomic profiles of these subsets were determined. The direct antitumor efficacy and the potential of enhancing antitumor immunity of the strategy using the ATR-TOP1-inhibitor combination were tested in SCLC cell lines.
resultsThe intrinsic expression of STING was significantly reduced in SCLC compared to normal lung tissues (p < 0.0001). Three STING-related SCLC subtypes were identified in which the STING-high subtype was associated with (1) high immune infiltration, (2) high expression of genes related to MHC and immune checkpoints, and (3) high EMT and ferroptosis score. On the contrary, the STING-low subtype was enriched with pathways related to DNA damage response (DDR) and cell cycle progression. The association between the DDR pathway activity and the STING-IFN innate immune response was verified by in vitro experiments in which the inhibition of ATR and TOP1 triggered the expression of genes encoding type I IFN signaling and pro-inflammatory cytokines/chemokines in a STING-low SCLC cell line.
conclusionOur study verifies that activation of the STING-IFN response by ATR and TOP1 inhibitors might be a therapeutic strategy to improve the response to immune checkpoint therapy in STING-low SCLC. Furthermore, the combinations of ATR and TOP1 inhibitors can augment tumor inflammation in STING-low SCLC.
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