ArticleJCI insight2023
Mutant RB1 enhances therapeutic efficacy of PARPis in lung adenocarcinoma by triggering the cGAS/STING pathway.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- A model of cellular proliferation and mitochondrial biogenesis predicts prognosis and immunotherapy response in lung adenocarcinoma.Translational cancer research · 2026Article
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- RNA-binding protein RALYL-mediated BCL11B RNA stability promotes immune escape in small cell lung cancer through transcriptional activation of BUB3.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- PD-1⁺ CD8⁺ T cells: roles of PD-1 beyond an exhaustion marker.Seminars in immunopathology · 2026Review
- RNF8 Relieves asthma-induced DNA Damage and Ferroptosis in Airway Epithelial Cells Through the AKT-NRF2 Axis.Applied biochemistry and biotechnology · 2026Article
- A machine learning-driven framework integrating cell death and senescence signatures for multi-target drug design and immunotherapy optimization in ovarian cancer.NPJ precision oncology · 2026Article
- Post-translational modifications in retinoblastoma: mechanisms, immune regulation, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Prognostic value and biological role of STING-related genes GAB3 and IL16 in lung adenocarcinoma: implications for immune evasion and treatment.Scientific reports · 2025Article
- High-grade glioma with pleomorphic and pseudopapillary features: a single-institution series of three cases.Acta neuropathologica communications · 2025Article
- Harnessing single-cell and multi-omics insights: STING pathway-based predictive signature for immunotherapy response in lung adenocarcinoma.Frontiers in immunology · 2025Article
- Analysis of pathogenic variants in retinoblastoma reveals a potential gain of function mutation.Genes & cancer · 2025Article
- Therapeutic Strategies for RB1-Deficient Cancers: Intersecting Gene Regulation and Targeted Therapy.Cancers · 2024Review
- Targeting the cGAS-STING Pathway Inhibits Peripheral T-cell Lymphoma Progression and Enhances the Chemotherapeutic Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly (ADP-ribose) polymerase inhibitors (PARPis) are approved for cancer therapy according to their synthetic lethal interactions, and clinical trials have been applied in non-small cell lung cancer. However, the therapeutic efficacy of PARPis in lung adenocarcinoma (LUAD) is still unknown. We explored the effect of a mutated retinoblastoma gene (RB1) on PARPi sensitivity in LUAD. Bioinformatic screening was performed to identify PARPi-sensitive biomarkers. Here, we showed that viability of LUAD cell lines with mutated RB1 was significantly decreased by PARPis (niraparib, rucaparib, and olaparib). RB1 deficiency induced genomic instability, prompted cytosolic double-stranded DNA (dsDNA) formation, activated the cGAS/STING pathway, and upregulated downstream chemokines CCL5 and CXCL10, triggering immune cell infiltration. Xenograft experiments indicated that PARPi treatment reduced tumorigenesis in RB1-KO mice. Additionally, single-cell RNA sequencing analysis showed that malignant cells with downregulated expression of RB1 had more communications with other cell types, exhibiting activation of specific signaling such as GAS, IFN response, and antigen-presenting and cytokine activities. Our findings suggest that RB1 mutation mediates the sensitivity to PARPis through a synthetic lethal effect by triggering the cGAS/STING pathway and upregulation of immune infiltration in LUAD, which may be a potential therapeutic strategy.
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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 OpenQuestion graph.