REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1628937
This article is part of the Research TopicCommunity Series in Tumor Microenvironment and Metabolic Reprogramming in Cancer: Volume IIView all 6 articles
Harnessing glycolysis in gastric cancer: molecular targets, therapeutic strategies, and clinical horizons
Provisionally accepted
Zexing Shan
Yefu Liu*- Liaoning Cancer Hospital, China Medical University, Shenyang, China
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Gastric cancer (GC) continues to rank among the leading causes of cancerrelated mortality globally, with treatment resistance and recurrence posing significant clinical hurdles. While surgical interventions, chemotherapy, and targeted therapies are available, their efficacy in managing advanced or metastatic forms of the disease remains constrained. This review provided an overview of the role of glycolytic reprogramming in gastric cancer, emphasizing the complex regulation by epigenetic mechanisms, non-coding RNAs, post-translational modifications, and oncogenic signaling pathways. This review discusses how epigenetic mechanisms, including m6A methylation and ceRNA networks involving circRNAs and microRNAs, modulate key glycolytic enzymes such as PKM2, HK2, and PGK1, thereby promoting tumor growth, metastasis, and chemoresistance. The study also emphasizes the impact of post-translational modifications like succinylation and ubiquitination on enzyme activity, affecting glycolytic flux and tumor adaptability. Additionally, the article details the crosstalk between glycolytic pathways and oncogenic signaling networks, including hypoxia-inducible factors and YAP/TAZ transcriptional regulators, which sustain tumor stemness and immune evasion. Therapeutic strategies targeting these metabolic vulnerabilitiessuch as inhibiting m6A regulators, disrupting ceRNA interactions, and modulating enzyme modificationsare discussed as potential approaches to improve gastric cancer treatment. Overall, we underscores the complexity of metabolic regulation in gastric cancer and proposes that targeting its epigenetic and signaling networks offers promising avenues for innovative therapies to overcome resistance and hinder tumor progression.
Keywords: gastric cancer, Glycolytic metabolic reprogramming, Lactate, Tumor Microenvironment, Therapeutic targeting
Received: 15 May 2025; Accepted: 11 Jul 2025.
Copyright: © 2025 Shan and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yefu Liu, Liaoning Cancer Hospital, China Medical University, Shenyang, China
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