2. Academic Validation
  3. Individualized drug screening in cholangiocarcinoma using organoid models and patient-derived tumor xenograft

Individualized drug screening in cholangiocarcinoma using organoid models and patient-derived tumor xenograft

  • BMC Cancer. 2025 Dec 31;26(1):173. doi: 10.1186/s12885-025-15495-w.
Pinsheng Han # 1 2,  Liuyang Zhu # 3,  Wen Tong # 4,  Sen Liu 5,  Yongdeng Xu 2,  Libo Wang 2,  Tianze Wang 1,  Tianyu Zhao 2,  Yu Miao 2,  Hao Chi 6,  Tao Cui 7,  Ze Wang 8,  Long Yang 9,  Yamin Zhang 10
Affiliations

Affiliations

  • 1 School of Medicine, Nankai University, Tianjin, 300071, China.
  • 2 State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China.
  • 3 Department of Hepatobiliary Surgery, School of Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, 300384, China.
  • 4 Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
  • 5 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 6 First Central Clinical College of Tianjin Medical University, Tianjin, 300192, China.
  • 7 Hefei Tianhui Biotechnology Co., Ltd, Hefei, 230000, China.
  • 8 State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China. [email protected].
  • 9 Department of Hepatobiliary Surgery, School of Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, 300384, China. [email protected].
  • 10 Department of Hepatobiliary Surgery, School of Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, 300384, China. [email protected].
  • # Contributed equally.
PMID: 41469951 DOI: 10.1186/s12885-025-15495-w
Abstract

Introduction: 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.

Methods: Tumor 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.

Results: In 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.

Conclusions: Our findings indicate that the integration of PDO and PDX models can successfully guide clinical treatment strategies, facilitating effective personalized therapy for CCA patients.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12885-025-15495-w.

Keywords

Cholangiocarcinoma; Drug screening; Organoids; Patient-derived tumor xenograft; Whole exome sequencing.

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