Role of non-animal 3D models in H. pylori associated gastric carcinogenesis: Insights and future perspectives

Abstract

Three-dimensional (3D) gastric organoids have become valuable experimental models for gastric cancer research, as they closely mirror tumour architecture, molecular features, and treatment responses. Unlike two-dimensional cultures and animal models, gastric organoids capture key physiological and pathological characteristics of the human stomach, allowing more meaningful investigation of tumour development, host–microbe interactions, and epithelial–stromal crosstalk. These systems retain the genetic and phenotypic traits of their tissue of origin, making them suitable for both mechanistic studies and long-term experimentation.

This review outlines the development of gastric organoid technology, from early advances in adult stem cell–derived cultures to recent methodological refinements that have expanded their experimental and clinical relevance. We discuss how organoid models have helped address the challenge posed by the marked molecular and histological heterogeneity of gastric cancer, which continues to complicate diagnosis and therapeutics. In this regard, patient-derived gastric organoids and associated biobanks have shown strong potential as predictive tools for drug response, as they reliably preserve tumour structure and gene expression patterns observed in primary tissues. In addition, we highlight recent improvements in culture matrices and experimental approaches that have enhanced organoid robustness and reproducibility. The growing use of gastric organoids as preclinical platforms for drug screening and the study of cancer-related signaling pathways reflects the rapid maturation of the field. We consider current limitations, technical challenges, and future directions for gastric organoid research, emphasizing their role as complementary models that bridge the gap between conventional in vitro systems and in vivo studies in gastric cancer.