ArticleCancer research2024
CRISPR-Cas9 Screening Identifies KRAS-Induced COX2 as a Driver of Immunotherapy Resistance in Lung Cancer.
Article in Cancer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.Frontiers in immunology · 2025Pooled it
- The deubiquitinating enzyme USP42 promotes lung adenocarcinoma progression through PTGS2.Journal of molecular histology · 2026Article
- Cyclooxygenase-2 selective inhibitors in cancer prevention and therapy: inflammopharmacological basis and translational prospects.Medical oncology (Northwood, London, England) · 2026Review
- Chronic type II interferon promotes tumor growth through mitochondrial RNA-induced type I interferon and prostaglandin synthesis.Science (New York, N.Y.) · 2026Article
- KRAS Inhibitor-Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones.Cancer research · 2026Article
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- cPLA2α inhibition potentiates anti-PD-1 immunotherapy in lung adenocarcinoma via remodeling tumor microenvironment.Communications biology · 2026Article
- Functional analysis of the human miRNome in non-small cell lung cancer unveils a novel miR-92b-3p/NOTCH3 axis that drives tumor progression.Cell death & disease · 2026Article
- Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.International journal of molecular sciences · 2026Review
- Targeting Lipid Metabolic Reprogramming to Overcome Immunotherapy Resistance: Systemic Nutritional Modulation and Precision Nanomedicine.International journal of nanomedicine · 2026Review
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Integrated transcriptomic profiling reveals immune and molecular stage-specific signatures of colorectal cancer in hispanics living in Puerto Rico.Frontiers in immunology · 2026Article
- Elevated expression of ANAPC1 in lung squamous cell carcinoma: clinical implications and mechanisms.Future science OA · 2025Article
- Exploring the therapeutic role of thiabendazole in lung adenocarcinoma via network pharmacology and single-cell analysis.Translational oncology · 2025Article
- Blocking PCSK9 suppresses hepatocellular carcinoma immune escape by decreasing FLI1-mediated SPP1 and PD-L1 expression.Journal for immunotherapy of cancer · 2025Article
- Advances in RNA-based cancer therapeutics: pre-clinical and clinical implications.Molecular cancer · 2025Review
- Harnessing natural killer cell-related genes for prognostic and therapeutic advances in lung adenocarcinoma: a predictive model for survival and immunotherapy outcomes.Translational cancer research · 2025Article
- Orthotopically Implanted Murine Lung Adenocarcinoma Cell Lines for Preclinical Investigations.Cancers · 2025Review
- Biosafety considerations triggered by genome-editing technologies.Biosafety and health · 2025Review
- Advances in cancer immunotherapy: historical perspectives, current developments, and future directions.Molecular cancer · 2025Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Oncogenic KRAS impairs antitumor immune responses. As effective strategies to combine KRAS inhibitors and immunotherapies have so far proven elusive, a better understanding of the mechanisms by which oncogenic KRAS drives immune evasion is needed to identify approaches that could sensitize KRAS-mutant lung cancer to immunotherapy. In vivo CRISPR-Cas9 screening in an immunogenic murine lung cancer model identified mechanisms by which oncogenic KRAS promotes immune evasion, most notably via upregulation of immunosuppressive COX2 in cancer cells. Oncogenic KRAS potently induced COX2 in both mouse and human lung cancer, which was suppressed using KRAS inhibitors. COX2 acted via prostaglandin E2 (PGE2) to promote resistance to immune checkpoint blockade (ICB) in lung adenocarcinoma. Targeting COX2/PGE2 remodeled the tumor microenvironment by inducing proinflammatory polarization of myeloid cells and influx of activated cytotoxic CD8+ T cells, which increased the efficacy of ICB. Restoration of COX2 expression contributed to tumor relapse after prolonged KRAS inhibition. These results provide the rationale for testing COX2/PGE2 pathway inhibitors in combination with KRASG12C inhibition or ICB in patients with KRAS-mutant lung cancer. Significance: COX2 signaling via prostaglandin E2 is a major mediator of immune evasion driven by oncogenic KRAS that promotes immunotherapy and KRAS-targeted therapy resistance, suggesting effective combination treatments for KRAS-mutant lung cancer.
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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 OpenQuestion graph.