ArticleBritish journal of cancer2024
KRAS and TP53 co-mutation predicts benefit of immune checkpoint blockade in lung adenocarcinoma.
Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Prevalence and clinico-morphological correlates of STK11 mutations in a large cohort of NSCLC lung adenocarcinomas.Virchows Archiv : an international journal of pathology · 2026Article
- The AUTACE That Degrades KRAS and Engages CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrative proteomic characterization of human lung adenocarcinoma with KRAS G12 mutations reveals molecular pathogenesis.Journal of advanced research · 2026Article
- Novel strategy of pemetrexed combined with localized therapy: breakthrough impact of long-term maintenance regimen on patient survival-a case report.Journal of medical case reports · 2026Article
- Homeobox A10 in gastrointestinal malignancies: unraveling metastatic mechanisms and novel therapeutic opportunities.Cancer metastasis reviews · 2026Review
- cGAS-STING pathway in lung cancer and emerging therapeutic approaches.Drug discovery today · 2026Review
- Bright side of the dark genome: antigens for next-gen cancer vaccines.Journal for immunotherapy of cancer · 2026Review
- Unraveling the nexus: Tumor mutational burden, PD-L1 expression, and oncogenic alterations in non-small cell lung cancer cytology specimens.Cancer cytopathology · 2026Article
- Ultra-rare TP53 and KRAS variants predict survival in ICI-treated solid tumours.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Mutant p53 epigenetically rewires CXCL10 to promote CD8⁺ T-cell infiltration and enhance the anti-PD-1 response in advanced prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review).Oncology reports · 2026Review
- Targeting rare oncogenic mutations in resectable non-small cell lung cancer: emerging perioperative strategies.Journal of thoracic disease · 2026Review
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- Article
- Inflammatory-Molecular Clusters as Predictors of Immunotherapy Response in Advanced Non-Small-Cell Lung Cancer.Journal of clinical medicine · 2026Article
- Long-term survival in a patient with non-small cell lung cancer harboringFrontiers in medicine · 2026Article
- Targetable driver gene-tumor immune microenvironment axis in non-small cell lung cancer: from molecular pathological mechanisms to precision immunotherapy stratification strategies.Frontiers in immunology · 2026Review
- Genetic differences between primary colorectal cancer and its paired synchronous and metachronous metastases.International journal of cancer · 2026Article
- Durable response to sotorasib-based combination therapy in advanced lung adenocarcinoma harboring KRAS G12C and STK11 mutations: a case report.Frontiers in oncology · 2026Article
- Multi-omics analysis identifies TLRscore for prognostic prediction and highlights TLR8 in macrophage-mediated antitumor immunity of lung adenocarcinoma.Frontiers in immunology · 2026Article
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPredictive biomarkers in use for immunotherapy in advanced non-small cell lung cancer are of limited sensitivity and specificity. We analysed the potential of activating KRAS and pathogenic TP53 mutations to provide additional predictive information.
methodsThe study cohort included 713 consecutive immunotherapy patients with advanced lung adenocarcinomas, negative for actionable genetic alterations. Additionally, two previously published immunotherapy and two surgical patient cohorts were analyzed. Therapy benefit was stratified by KRAS and TP53 mutations. Molecular characteristics underlying KRASmut/TP53mut tumours were revealed by the analysis of TCGA data.
resultsAn interaction between KRAS and TP53 mutations was observed in univariate and multivariate analyses of overall survival (Hazard ratio [HR] = 0.56, p = 0.0044 and HR = 0.53, p = 0.0021) resulting in a stronger benefit for KRASmut/TP53mut tumours (HR = 0.71, CI 0.55-0.92). This observation was confirmed in immunotherapy cohorts but not observed in surgical cohorts. Tumour mutational burden, proliferation, and PD-L1 mRNA were significantly higher in TP53-mutated tumours, regardless of KRAS status. Genome-wide expression analysis revealed 64 genes, including CX3CL1 (fractalkine), as specific transcriptomic characteristic of KRASmut/TP53mut tumours.
conclusionsKRAS/TP53 co-mutation predicts ICI benefit in univariate and multivariate survival analyses and is associated with unique molecular tumour features. Mutation testing of the two genes can be easily implemented using small NGS panels.
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