Patient-derived gastric cancer organoids for functional precision oncology: disease-specific bottlenecks and clinical readiness

Gastric cancer (GC) poses a distinct modeling challenge. The disease varies by region, histology, metastatic site, and treatment history. It also develops within a gastric niche shaped by acid, mucus, polarity, microbes, and stroma. Patient-derived organoids (PDOs) can preserve tumor-linked epithelial states and support living biobanks. They also enable genotype-phenotype studies and functional testing of therapeutic vulnerabilities. Their clinical value depends on representation, not model complexity alone. The assay must also return clear results within a useful clinical window. This review evaluates GC PDOs as functional companion models for precision oncology rather than stand-alone treatment decision tools. We discuss four barriers that limit clinical readiness. Establishment bias reduces representation of diffuse-type, scirrhous, and signet-ring cell carcinomas. Standard organoid lumens do not reproduce gastric acidity, stratified mucus, or Helicobacter pylori-driven polarity loss. Long-term expansion can select culture-adapted clones and weaken clinical representativeness. PDO drug screening also remains difficult to align with urgent treatment timelines. Fresh-sample assays may shorten turnaround time but reduce scale and depth. We further highlight biological insights gained from GC organoids. These include niche independence, epigenetic dependencies, ARID1A-linked vulnerabilities, and chemotherapy resistance. We propose a readiness framework based on six criteria: tumor authenticity, subtype coverage, niche fidelity, turnaround time, assay standards, and outcome validation. This framework may help define where GC PDOs can support clinical reasoning.