Helicobacter pylori and hyperglycemia fuel gastric cancer glycolysis - Mechanisms and targeted intervention

Sep 22, 2026

Helicobacter pylori (H. pylori) infection is a Gram-negative bacterial risk factor for gastric cancer, driving chronic gastritis and increasing malignant potential. Glycolysis is central to gastric cancer metabolism, supplying energy and supporting rapid proliferation, especially under hypoxia. Enhanced H. pylori-driven glycolysis increases lactate output and reshapes the tumor microenvironment into a more acidic niche that favors progression. The review synthesizes glycolysis mechanisms and highlights metabolism-targeted therapeutic opportunities.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Combined effect of H. pylori and hyperglycemia in the pathogenesis of gastric cancer

Tumor microenvironment (TME)

H. pylori and glycolysis

Comprehensive overview of glycolysis-related therapeutic targets

Summary and future research directions

INTERNATIONAL JOURNAL OF MOLEcULAR MEdIcINE 57: 92, 2026 Helicobacter pylori and hyperglycemia fuel gastric cancer glycolysis: Mechanisms and targeted intervention (Review) 1‑3* 1‑3* 2 2 2 2 2 YOUJIA LIU , FANG WANG , YA dENG , YANxIA HU , FEIHONG SHU , JIE YU , GUOYOU GOU , MIN WEN2 , cHEN LUO2 , xIANMIN LU2 , QIAN dU 1 , JINGYU xU2 and RUI xIE 1,3 1 department of Endoscopy and digestive System, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. china; 2collaborative Innovation center for Tissue Repair and Regenerative Medicine, Zunyi Medical University, Zunyi, 3 Guizhou 563006, P.R. china; Guizhou Provincial Key Laboratory for digestive System diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550002, P.R. China Received May 31, 2025; Accepted November 28, 2025 DOI: 10.3892/ijmm.2026.5763 Abstract. Helicobacter pylori (H. pylori) is a Gram‑negative bacterial pathogen, and infection with this pathogen is a primary risk factor for gastric cancer (Gc), often inducing chronic gastritis, which further increases the risk of cancer. Glycolysis carries out a key role in Gc metabolism, serving as the primary energy pathway for cancer cells, particularly under hypoxic conditions . Enhanced glycolysis allows Gc cells to sustain high proliferation rates and produce lactic acid, creating an acidic tumor microenvironment that promotes tumor progression. Understanding the mechanisms of H. pylori‑driven glycolysis may provide new insights into Correspondence to: Professor Jingyu xu, collaborative Innovation center for Tissue Repair and Regenerative Medicine, Zunyi Medical University, 1 campus Road, Zunyi, Guizhou 563006, P.R. china E‑mail: [xujingyu_gzzy@126.com](xujingyu_gzzy@126.com) Professor Rui xie, department of Endoscopy and digestive System, Guizhou Provincial People's Hospital, 395 Jinzhu East Road, Guiyang, Guizhou 550002, P.R. china E‑mail: [xr19841029@aliyun.com](xr19841029@aliyun.com) *contributed equally Abbreviations: H. pylori, Helicobacter pylori; Gc , gastric cancer; cagA, cytotoxin‑associated gene A; cag PAI, cag pathogenicity island; VacA, vacuolating cytotoxin A; IGF, insulin‑like growth factor; IR‑A, insulin receptor isoform A; ROS, reactive oxygen species; TME, tumor microenvironment; EcM, extracellular matrix; TAMs, tumor‑associated macrophages; PdK1, 3‑phosphoinositide‑dependent protein kinase 1; cAF, cancer‑associated fibroblasts; EMT, epithelial‑mesenchymal transition; GLUT, glucose transporter; HK2, hexokinase 2; OxPHOS, oxidative phosphorylation; ETc , electron transport chain; TcA cycle, tricarboxylic acid cycle; LdH, lactate dehydrogenase; PKM2, pyruvate kinase M2; 5‑FU, 5‑fluorouracil Key words: gastric cancer, metabolic reprogramming, Helicobacter pylori infection, Warburg effect, glycolysis, metabolism‑targeted therapy, tumor microenvironment Gc pathogenesis and reveal novel therapeutic targets . The present review addresses advances in glycolysis research in Gc , summarizing its characteristics, identifying key media‑ tors involved in metabolic reprogramming and exploring potential molecular mechanisms to recommend new targets for therapy. Contents 1. Introduction 2. combined effect of H. pylori and hyperglycemia in the pathogenesis of Gc 3. TME 4. H. pylori and glycolysis 5. comprehensive overview of glycolysis‑related therapeutic targets 6. Summary and future research directions 1. Introduction Gc is a global health issue. According to 2022 GLOBOcAN data, Gc ranks as the 5th most common malignancy world‑ wide and is a leading cause of cancer‑related mortality (1) . In china, the incidence of Gc is the 5th highest compared with all types of cancer (2,3). Helicobacter pylori (H. pylori) infection is recognized as one of the most pronounced patho‑ genic factors for Gc. In 1994, the International Agency for Research on cancer of the World Health Organization clas‑ sified H. pylori as a Group 1 (definite) c

FAQs

How does Helicobacter pylori contribute to gastric cancer risk?

H. pylori infection is recognized as a prominent pathogenic factor for gastric cancer, including via chronic gastritis that elevates cancer risk.

Why is glycolysis important for gastric cancer cells?

Glycolysis is described as a key energy pathway and metabolic program that supports high proliferation, including lactate production that promotes a tumor-favoring acidic microenvironment.

What therapeutic strategy is proposed based on glycolysis mechanisms?

The review focuses on identifying glycolysis-related mechanisms and key mediators of metabolic reprogramming, recommending novel molecular targets for metabolism-targeted therapy.

Sep 22, 2026

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