Evolving Molecular Subtypes of Gastric Cancer - From Past Classifications to Present Consensus and Future Directions for Precision Therapy

Sep 22, 2026

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Gastric cancer is a biologically heterogeneous disease, and high-throughput multiomic technologies have enabled decomposition into distinct, more homogeneous molecular subtypes. Early gene-expression, methylation, and histology classifications laid groundwork for multi-omic frameworks from The Cancer Genome Atlas and Asian Cancer Research Group, culminating in clinically relevant consensus models. Established biomarkers guide targeted therapy and immune checkpoint inhibitors, while single-cell and spatial analyses refine tumor microenvironment understanding and evolutionary trajectories. The review connects subtype evolution to precision therapy.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Abstract

Introduction

Molecular Subtypes of Gastric Cancer

J Gastric Cancer. 2026 Jan;26(1):16-30 [https://doi.org/10.5230/jgc.2026.26.e12](https://doi.org/10.5230/jgc.2026.26.e12)[ ](https://doi.org/10.5230/jgc.2026.26.e12)pISSN 2093-582X·eISSN 2093-5641 Review Article Received: Oct 30, 2025 Revised: Dec 9, 2025 Accepted: Dec 9, 2025 Published online: Jan 5, 2026 Correspondence to Ju-Seog Lee Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA. Email: [jlee@mdanderson.org](jlee@mdanderson.org) Copyright © 2026. Korean Gastric Cancer Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://](https://)[ ](https://)[creativecommons.org/licenses/by-nc/4.0](creativecommons.org/licenses/by-nc/4.0)) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ORCID iDs Ju-Seog Lee [https://orcid.org/0000-0002-5666-9753](https://orcid.org/0000-0002-5666-9753) Funding This study was supported by the Cancer Prevention and Research Institute of Texas Individual Investigator Research Award (RP170307), Congressionally Directed Medical Research Programs Peer-Reviewed Cancer Research Program Award (CA160616), and the National Cancer Institute (R01-CA237327 and P50-CA217674) . Conflict of Interest No potential conflict of interest relevant to this article was reported. Evolving Molecular Subtypes of Gastric Cancer: From Past Classifications to Present Consensus and Future Directions for Precision Therapy Ju-Seog Lee Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA ABSTRACT Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multiomic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal growth factor receptor 2 amplification, microsatellite instability, and programmed death-ligand 1 expression are now used clinically to guide treatment with targeted agents and immune checkpoint inhibitors. Emerging single-cell and spatial transcriptomic analyses have further refined this landscape by deconstructing tumor microenvironments and potential evolutionary trajectories associated with disease progression. This review examines the evolution of molecular classification systems for gastric cancer, highlights current consensus frameworks, and discusses how subtype-based stratification will transform clinical trial design and enable biomarker-driven precision therapy. Keywords: Genomics; Classification; Diagnosis; Biomarkers INTRODUCTION Gastric cancer remains one of the most prevalent and lethal malignancies worldwide. Despite declining incidence in some Western countries, gastric cancer continues to be the fifth most common cancer and the fourth leading cause of cancer-related mortality globally, accounting for over one million new cases and nearly 660,000 deaths annually [1,2] . This disease burden is disproportionately concentrated in East Asia, particularly Korea, Japan, and China, where standardized screening programs and endoscopic detection have enabled earlier diagnosis and improved survival compared with Western populations [3,4]. However, in several low-and middle-income regions, including Lat

FAQs

What has multiomic research changed in gastric cancer classification?

High-throughput multiomic technologies break gastric cancer into distinct molecular subtypes, replacing a single-entity view with a more biologically stratified framework.

Which organizations and models contributed to modern molecular taxonomy?

Foundational multi-omic frameworks were proposed by The Cancer Genome Atlas and Asian Cancer Research Group, and integrative efforts such as the Consensus Genomic Subtypes (Super 6) model unified information into clinically relevant subtypes.

How are biomarkers used in current gastric cancer treatment decisions?

Established biomarkers including HER2 amplification, microsatellite instability, and PD-L1 expression are used clinically to guide targeted agents and immune checkpoint inhibitor therapy.

Sep 22, 2026

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