Patient-derived organoids for precise medicine in gastric cancer

Gastric cancer (GC) is a challenging malignant disease among gastrointestinal tumors. The clinical treatments for GC include surgery, neoadjuvant therapy and adjuvant chemotherapy. As patients' response to chemotherapeutic drugs varies, an approach to predict the efficacy of chemotherapeutic treatment is urgently needed. Here, a biorepository of 17 human gastric tumor organoids (GTOs) and 9 normal organoids (GNOs) derived from GC patients was established, which contains the intestinal, diffuse and mixed-type of GC. GTOs retained morphologic, histopathological and genetic features of the tumors from which they were derived, and patient-derived organoid xenograft model indicated tumorigenicity of organoids. GTOs responses to clinically respective chemotherapy treatment positively correlated with the individual patient's clinical response. Meanwhile, GNOs, which maintained original characteristics of corresponding tissues, could be separated from GTOs. The use of GNOs predicted the cytotoxic effect of chemotherapy on the organism. Our study implies that patient-derived organoids predict GC patient responses to chemotherapy and provide a solution for personalized treatment. Overall design: In order to investigate the molecular characteristics of GTOs, we performed whole exome sequencing on tumor tissues and GTOs derived from 8 patients to explore the genomic landscape and identify genetic alterations in GTOs compared to their corresponding tumor tissues. By comparing these findings to the corresponding drug screening outcomes using organoids, we aim to elucidate the molecular evolution of GTOs and shed light on their potential as models for precision medicine applications in cancer research and therapy.