Individualized drug screening in cholangiocarcinoma using organoid models and patient-derived tumor xenograft
摘要
Cholangiocarcinoma (CCA) is a highly aggressive biliary malignancy with a very poor prognosis. How to screen the optimal chemotherapy regimen is crucial for enhancing the prognosis of CCA patients. The study aims to develop patient-derived tumor organoid (PDO) models and patient-derived tumor xenograft (PDX) models of CCA to simulate clinical responses to chemotherapy.
MethodsTumor tissues were collected from patients undergoing surgical resection and subsequently utilized to establish PDO and PDX models. Hematoxylin-eosin (H&E), immunohistology (IHC), and immunofluorescence (IF) were conducted to analyze the biological characteristics of these PDXs and PDOs. Whole exome sequencing (WES) was performed to identify the mutation types of primary tumor, PDO, and PDX. Drug sensitivity assays were conducted utilizing PDO and PDX models to compare clinical treatment responses.
ResultsIn this study, we successfully established 18 PDO (success rate, 56.3%) models and 21 PDX models (success rate, 65.6%) from 32 patients diagnosed with CCA. PDO and PDX preserved the mutational profiles characteristic of the primary tumor samples. The drug screening results from PDOs demonstrated a correlation with the actual clinical response to chemotherapy regimens, and these findings were further validated in PDX models.
ConclusionsOur findings indicate that the integration of PDO and PDX models can successfully guide clinical treatment strategies, facilitating effective personalized therapy for CCA patients.