Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Abstract Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with limited treatment options in advanced stages. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting PD1/PD-L1, has emerged as promising therapeutic approach. However, significant proportion patients exhibit primary or acquired resistance, limiting the overall efficacy immunotherapy. This review provides comprehensive analysis mechanisms underlying immunotherapy resistance GC, including role tumor microenvironment, dynamic PD-L1 expression, compensatory activation other checkpoints, and genomic instability. Furthermore, explores GC-specific factors such molecular subtypes, unique evasion mechanisms, impact Helicobacter pylori infection. We also discuss emerging strategies to overcome combination therapies, novel immunotherapeutic approaches, personalized based on genomics microenvironment. By highlighting these key areas, this aims inform future research directions clinical practice, ultimately improving outcomes for GC undergoing

Language: Английский

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SMR-guided molecular subtyping and machine learning model reveals novel prognostic biomarkers and therapeutic targets in non-small cell lung adenocarcinoma

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 10, 2025

Non-small cell lung adenocarcinoma (LUAD) is a markedly heterogeneous disease, with its underlying molecular mechanisms and prognosis prediction presenting ongoing challenges. In this study, we integrated data from multiple public datasets, including TCGA, GSE31210, GSE13213, encompassing total of 867 tumor samples. By employing Mendelian randomization (MR) analysis, machine learning techniques, comprehensive bioinformatics approaches, conducted an in-depth investigation into the characteristics, prognostic markers, potential therapeutic targets LUAD. Our analysis identified 321 genes significantly associated LUAD, CENP-A, MCM7, DLGAP5 emerging as highly connected nodes in network analyses. performing correlation Cox regression 26 classified LUAD samples two subtypes distinct survival outcomes. The Random Survival Forest (RSF) model exhibited robust predictive capabilities across independent cohorts (AUC > 0.75). Beyond merely predicting patient outcomes, also captures key features immune microenvironment responses. Functional enrichment revealed complex interplay cycle regulation, DNA repair, response, metabolic reprogramming progression Furthermore, observed strong between risk scores expression specific cytokines, such CCL17, CCR2, CCL20, suggesting novel avenues for developing cytokine network-based strategies. This study offers fresh insights subtyping, prediction, personalized decision-making laying critical foundation future clinical applications targeted therapy research.

Language: Английский

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Integrative analysis of single-cell and bulk RNA sequencing reveals the oncogenic role of ANXA5 in gastric cancer and its association with drug resistance

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 7, 2025

Background Gastric cancer (GC) remains a leading cause of cancer-related mortality, with over one million new cases and 769,000 deaths reported in 2020. Despite advancements chemotherapy, surgery, targeted therapies, delayed diagnosis due to overlooked early symptoms leads poor prognosis. Methods We integrated bulk RNA sequencing single-cell datasets from TCGA, GEO, OMIX001073, employing normalization, batch effect correction, dimensionality reduction methods identify key cell populations associated GC invasion epithelial-mesenchymal transition (EMT), as well analyze the tumor immune microenvironment. Results Our analysis identified MUC5AC+ malignant epithelial cluster significant player EMT. Cluster 1, representing this population, exhibited higher EMT scores compared other clusters. Survival showed that high abundance 0 correlated improved survival rates (P=0.012), whereas 1 was poorer outcomes (P=0.045). A prognostic model highlighted ANXA5 GABARAPL2 two critical genes upregulated tumors. High-risk patients demonstrated increased infiltration worse prognosic. Analysis mutation burden (TMB) indicated low TMB high-risk group had worst Wet-lab validation experiments confirmed oncogenic role ANXA5, showing its facilitation proliferation, invasion, migration while suppressing apoptosis. Conclusion This study offers novel insights into subpopulations cells their roles progression. It provides potential therapeutic targets combat GC, contributing crucial understanding fundamental mechanisms drug resistance gastrointestinal cancers.

Language: Английский

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A New Medical Evaluation for Gastric Cancer Patients to Increase the Success Rate of Immunotherapy: A 2024 Update

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1121 - 1121

Published: Aug. 24, 2024

Researchers have performed numerous studies on immunotherapy because of the high death rate associated with gastric cancer (GC). GC research has made tremendous progress, and we wanted to provide an update this topic. On basis update, suggest performing a new medical evaluation before initiating in patients increase success immunotherapies. We propose that start immunotherapy, they should be evaluated given score one two points for following factors: immunopathological features, molecular genomic potential consequences bacterial pathogens, immunotherapeutic resistance hyperprogressive illness, use biomarkers gauge their prognosis responses optimize surgery. The proposed scoring system could also help diagnosis GC. With all advances genetics, immunology, microbiology, improved, not changed. Currently, diagnosed undergo surgical resection as only permanent solution. Patients who meet maximum from presented proposal eligible immediately after immunotherapy. Therefore, first-line option clinicians.

Language: Английский

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