Related Experiment Video
Updated: Dec 26, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine
Jennifer L Leiting1, Stephen J Murphy2, John R Bergquist1
1Department of Surgery, Mayo Clinic, Rochester, MN.
Background & Aims:
Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Due to their low incidence, research into effective therapeutics has been limited. Novel research platforms for pre-clinical studies are desperately needed. We sought to develop a patient-derived biliary tract cancer xenograft catalog.
Methods:
With appropriate consent and approval, surplus malignant tissues were obtained from surgical resection or radiographic biopsy and implanted into immunocompromised mice. Mice were monitored for xenograft growth. Established xenografts were verified by a hepatobiliary pathologist. Xenograft characteristics were correlated with original patient/tumor characteristics and oncologic outcomes. A subset of xenografts were then genomically characterized using Mate Pair sequencing (MPseq).
Results:
Between October 2013 and January 2018, 87 patients with histologically confirmed biliary tract carcinomas were enrolled. Of the 87 patients, 47 validated PDX models were successfully generated. The majority of the PDX models were created from surgical resection specimens (n = 44, 94%), which were more likely to successfully engraft when compared to radiologic biopsies (p = 0.03). Histologic recapitulation of original patient tumor morphology was observed in all xenografts. Successful engraftment was an independent predictor for worse recurrence-free survival. MPseq showed genetically diverse tumors with frequent alterations of CDKN2A, SMAD4, NRG1, TP53. Sequencing also identified worse survival in patients with tumors containing tetraploid genomes.
Conclusions:
This is the largest series of biliary tract cancer xenografts reported to date. Histologic and genomic analysis of patient-derived xenografts demonstrates accurate recapitulation of original tumor morphology with direct correlations to patient outcomes. Successful development of biliary cancer tumografts is feasible and may be used to direct subsequent therapy in high recurrence risk patients.
Lay Summary:
Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients.
Insights
This study created the largest catalog of patient-derived biliary tract cancer xenografts. These models accurately reflect patient tumors and can predict outcomes, aiding in personalized treatment for biliary tract cancers.
Area of Science:
- Oncology
- Cancer Research
- Translational Medicine
Background:
- Biliary tract cancers are rare, aggressive malignancies with limited treatment options and poor prognoses.
- Effective pre-clinical research models are crucial for advancing therapeutic development in biliary tract cancers.
- This study aimed to establish a patient-derived xenograft (PDX) catalog for biliary tract cancer research.
Purpose of the Study:
- To develop and characterize a comprehensive catalog of patient-derived biliary tract cancer xenografts.
- To assess the feasibility of generating PDX models from patient tumor samples.
- To correlate xenograft characteristics with patient outcomes and genomic profiles.
Main Methods:
- Surgically resected or biopsied biliary tract tumor tissues were implanted into immunocompromised mice.
- Xenograft growth was monitored, and established models were histologically verified by a hepatobiliary pathologist.
- Genomic characterization of a subset of xenografts was performed using Mate Pair sequencing (MPseq).
Main Results:
- 47 validated patient-derived xenograft models were generated from 87 enrolled patients.
- Models derived from surgical resections showed higher successful engraftment rates compared to biopsies (p=0.03).
- All xenografts accurately recapitulated the histology of the original patient tumors; successful engraftment predicted worse recurrence-free survival.
- Genomic analysis revealed frequent alterations in CDKN2A, SMAD4, NRG1, and TP53, with tetraploid genomes correlating with worse survival.
Conclusions:
- This study presents the largest series of biliary tract cancer xenografts to date.
- Patient-derived xenografts accurately reflect tumor morphology and correlate with patient outcomes.
- The successful development of these tumografts offers a valuable resource for guiding individualized therapy in high-risk biliary tract cancer patients.
More Related Videos
06:06High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts
Published on: December 20, 2024
04:49Creating Matched In vivo/In vitro Patient-Derived Model Pairs of PDX and PDX-Derived Organoids for Cancer Pharmacology Research
Published on: May 5, 2021