ArticleBMC medicine2022
Mutations of PI3K-AKT-mTOR pathway as predictors for immune cell infiltration and immunotherapy efficacy in dMMR/MSI-H gastric adenocarcinoma.
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06004713 (Multi-center, Non-interventional, Prospective Registry Study on the Treatment of Solid Tumors With Mismatch Repair Deficiency or Microsatellite Instability), which is not on this map. Cited by 58 papers.
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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.
Multi-center, Non-interventional, Prospective Registry Study on the Treatment of Solid Tumors With Mismatch Repair Deficiency or Microsatellite Instability
Who cites it
58 citing papers in PubMed, 85 citations in OpenAlex.
- PD-1 antibody camrelizumab plus apatinib and SOX as first-line treatment in patients with AFP-producing gastric or gastro-esophageal junction adenocarcinoma (CAP 06): a multi-center, single-arm, phase 2 trial.Signal transduction and targeted therapy · 2025Trial
- Impaired TGF-β signaling via AHNAK family mutations elicits an esophageal cancer subtype with sensitivities to genotoxic therapy and immunotherapy.Cancer immunology, immunotherapy : CII · 2024Trial
- Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction.PloS one · 2023Trial
- Long-Term Outcomes and Surgical Conversion After Immunotherapy in Microsatellite Instability-H Biliary Tract Cancers.JCO precision oncology · 2026Observational
- Unraveling the link between genomic instability and tumor immune evasion in oral squamous cell carcinoma: Role of CBMN assay and emerging perspectives.Medical oncology (Northwood, London, England) · 2026Review
- The evolving role of OMICS in gastrointestinal tumor biology and clinical practice.Molecular cancer · 2026Review
- Linavonkibart and pembrolizumab in immune checkpoint blockade-resistant advanced solid tumors: a phase 1 trial.Nature medicine · 2026Article
- Early- and advanced-stage MSI-H non-colorectal cancers: best management and challenges in 2025.ESMO gastrointestinal oncology · 2026Review
- NCAPD2 Modulates MHC-I Antigen Presentation via the PI3K/AKT Axis to Drive Metastatic Progression in Gastric Cancer.Digestive diseases and sciences · 2026Article
- Mechanisms and therapeutic strategies for immunotherapy resistance in gastric cancer.Cancer cell international · 2025Review
- Article
- TSC2-mutated perivascular epithelioid cell tumor with partial response to mTOR inhibition: a case report and literature review.Discover oncology · 2025Article
- Systematic benchmarking of large Language models in programmed cell death-oriented gastric cancer research: a comparative analysis of DeepSeek‑V3, DeepSeek‑R1, and Claude 3.5.Discover oncology · 2025Article
- Immunotyping the Tumor Microenvironment Reveals Molecular Heterogeneity for Personalized Immunotherapy in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular Interplay Between PTEN, ARID1A, PD-L1, and MMR in Asian Ovarian Clear Cell Carcinoma: Implications for Immunotherapy Response and Patient Stratification.International journal of molecular sciences · 2025Article
- Oncogenic Signalling Pathways in Cancer Immunotherapy: Leader or Follower in This Delicate Dance?International journal of molecular sciences · 2025Review
- Comparison of clinicopathological parameters with the presence of Epstein-Barr virus and the absence of DNA mismatch repair proteins in gastric adenocarcinomas.Asian biomedicine : research, reviews and news · 2025Article
- Mutation Analysis of TMB-High Colorectal Cancer: Insights Into Molecular Pathways and Clinical Implications.Cancer science · 2025Article
- Integrative analysis of bulk and single-cell sequencing reveals TNFSF9 as a potential regulator in microsatellite instability stomach adenocarcinoma.European journal of medical research · 2025Article
- Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA significant subset of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric adenocarcinomas (GAC) are resistant to immune checkpoint inhibitors (ICIs), yet the underlying mechanism remains largely unknown. We sought to investigate the genomic correlates of the density of tumor-infiltrating immune cells (DTICs) and primary resistance to ICI treatment.
methodsFour independent cohorts of MSI-H GAC were included: (i) the surgery cohort (n = 175) with genomic and DTIC data, (ii) the 3DMed cohort (n = 32) with genomic and PD-L1 data, (iii) the Cancer Genome Atlas (TCGA) cohort (n = 73) with genomic, transcriptomic, and survival data, and (iv) the ICI treatment cohort (n = 36) with pre-treatment genomic profile and ICI efficacy data.
resultsIn the dMMR/MSI-H GAC, the number of mutated genes in the PI3K-AKT-mTOR pathway (NMP) was positively correlated with tumor mutational burden (P < 0.001) and sensitivity to PI3K-AKT-mTOR inhibitors and negatively correlated with CD3
conclusionsHigher NMP was identified as a potential predictor of lower DTICs and primary resistance to ICIs in the dMMR/MSI-H GAC. Our results highlight the possibility of using mutational data to estimate DTICs and administering the PI3K-AKT-mTOR inhibitor as an immunotherapeutic adjuvant in NMP-high subpopulation to overcome the resistance to ICIs.
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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.