Patient-derived gastric cancer organoids for functional precision oncology: disease-specific bottlenecks and clinical readiness.
4 affiliations
- 1Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China; Department of Medicinal Chemistry, School of Pharmacy, Qingdao University, Qingdao, 266071, China.
- 2Department of General Surgery, The Affiliated Hospital of Qingdao University, Gastrointestinal Tumor Translational Medicine Research Institute of Qingdao University, Qingdao, Shandong, China.
- 3Department of Medicinal Chemistry, School of Pharmacy, Qingdao University, Qingdao, 266071, China. Electronic address: [email protected].
- 4Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China. Electronic address: [email protected].
Abstract
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.
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BibTeX
@article{mi2026patientderived,
title = {{Patient-derived gastric cancer organoids for functional precision oncology: disease-specific bottlenecks and clinical readiness.}},
author = {Chenyang Mi and Xuechao Liu and Xiaowen Tang and Guoliang Li},
journal = {Translational oncology},
year = {2026},
month = oct,
doi = {10.1016/j.tranon.2026.103065},
url = {https://europepmc.org/article/MED/42868714},
note = {CC BY},
}
RIS
TY - JOUR
TI - Patient-derived gastric cancer organoids for functional precision oncology: disease-specific bottlenecks and clinical readiness.
AU - Chenyang Mi
AU - Xuechao Liu
AU - Xiaowen Tang
AU - Guoliang Li
PY - 2026
DA - 2026/10/13
JO - Translational oncology
DO - 10.1016/j.tranon.2026.103065
UR - https://europepmc.org/article/MED/42868714
AB - 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.
SN - 1936-5233
ER -