Screening of an individualized treatment strategy for an advanced gallbladder cancer using patient-derived tumor xenograft and organoid models

Abstract

Gallbladder cancer is a highly aggressive malignancy with poor sensitivity to postoperative radiotherapy or chemotherapy; therefore, the development of individualized treatment strategies is paramount to improve patient outcomes. Both patient-derived tumor xenograft (PDX) and patient-derived tumor organoid (PDO) models derived from surgical specimens can better preserve the biological characteristics and heterogeneity of individual original tumors, display a unique advantage for individualized therapy and predicting clinical outcomes. In this study, PDX and PDO models of advanced gallbladder cancer were established, and the consistency of biological characteristics between them and primary patient samples was confirmed using pathological analysis and RNA-sequencing. Additionally, we tested the efficacy of chemotherapeutic drugs, targeted drugs, and immune checkpoint inhibitors using these two models. The results demonstrated that gemcitabine combined with cisplatin induced significant therapeutic effects. Furthermore, treatment with immune checkpoint inhibitors elicited promising responses in both the humanized mice and PDO immune models. Based on these results, gemcitabine combined with cisplatin was used for basic treatment, and immune checkpoint inhibitors were applied as a complementary intervention for gallbladder cancer. The patient responded well to treatment and exhibited a clearance of tumor foci. Our findings indicate that the combined use of PDO and PDX models can guide the clinical treatment course for gallbladder cancer patients to achieve individualized and effective treatment.