Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer

Area of Science:

• Oncology
• Gastroenterology
• Genomics

Background:

• Chemotherapy efficacy in gastric cancer (GC) is highly variable.
• Predicting patient response to chemotherapy remains a clinical challenge.

Purpose of the Study:

• To establish patient-derived organoids (PDOs) for gastric cancer.
• To assess the utility of PDOs in predicting chemotherapy response.
• To identify gene expression biomarkers for chemosensitivity.

Main Methods:

• Established 57 gastric cancer patient-derived organoids (PDOs) from 73 patients.
• Performed RNA sequencing on PDOs to analyze gene expression.
• Validated PDO drug-response predictions in patient-derived organoids-based xenograft (PDOX) mouse models.
• Correlated PDO results with actual patient clinical responses.

Main Results:

• Gastric cancer PDOs retained histological characteristics and showed varied responses to chemotherapeutics.
• Identified distinct gene expression profiles associated with 5-fluorouracil (FU) or oxaliplatin sensitivity versus resistance.
• Developed gene expression biomarker panels with high accuracy (AUC >0.8) for predicting sensitivity to 5-FU and oxaliplatin.
• Achieved 91.7% concordance between PDO drug-response predictions and clinical outcomes in patients.

Conclusions:

• Gastric cancer PDOs serve as a reliable preclinical model for evaluating drug sensitivity.
• Gene expression biomarkers identified in PDOs can predict patient response to specific chemotherapies.
• PDOs offer a valuable tool for personalized medicine in gastric cancer treatment.