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Updated: Aug 27, 2025
Author Spotlight: Replicating Human Osteosarcoma Progression in Immunodeficient Mice for Cancer Study
Published on: March 22, 2024
Generation and characterization of patient-derived xenografts from patients with osteosarcoma
Fei Chen1, Zhenzhen Zhang2, Rongkai Shen1
1Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, 20, Chazhong Rd., Fuzhou, Fujian 350005, China.
Background:
Standard therapy of osteosarcoma (OS) rests on cytotoxic regimes, which dramatically limits the further improvement in the prognosis of patients with OS. Preclinical models of OS are extremely urgent to break this impasse.
Materials And Methods:
Here, we describe our experience of developing patient-derived tumor xenografts (PDXs) using surgical samples from patients with OS. All the xenografts growing subcutaneously in mice will be identified pathologically and genetically. Furthermore, we explored the consistency of the drug sensitivity between the PDX models and corresponding patients against specific regimens.
Results:
We generated nine OS PDXs from 21 surgical resections of primary OS tumors, with an engraftment rate of 42.9 %. Morphological and immunohistochemical (SATB2, MDM2, CDK4, and Ki67) studies and whole-exome sequencing showed a remarkable similarity between the patient's tumor and corresponding PDX, which was maintained over several passages in mice. A therapeutic combination of Pirarubicin and Cisplatin was tested against two OS PDX models, in which the corresponding patient was insensitive and sensitive to the regimen, respectively.
Conclusion:
The panel of OS PDX models faithfully mirrored morphologic and genetic features of OS, representing reliable models to test therapeutic approaches.
Insights
Patient-derived osteosarcoma (OS) xenografts were developed to overcome limitations of current cytotoxic therapies. These models accurately reflect patient tumors, enabling reliable testing of new therapeutic strategies for osteosarcoma.
Area of Science:
- Oncology
- Translational Research
- Preclinical Models
Background:
- Standard osteosarcoma (OS) treatment relies on cytotoxic chemotherapy, which has plateaued patient prognosis.
- Developing novel preclinical models is crucial for advancing OS treatment strategies.
Purpose of the Study:
- To establish and characterize patient-derived tumor xenografts (PDXs) for osteosarcoma (OS).
- To assess the fidelity of OS PDX models in recapitulating patient tumor characteristics.
- To evaluate the consistency of drug sensitivity between OS PDX models and their corresponding patients.
Main Methods:
- Generation of OS PDXs from surgical samples of primary OS tumors.
- Pathological and genetic characterization of xenografts, including morphology, immunohistochemistry (SATB2, MDM2, CDK4, Ki67), and whole-exome sequencing.
- Comparative drug sensitivity testing of PDX models and patients against Pirarubicin and Cisplatin regimens.
Main Results:
- Nine OS PDX models were successfully established from 21 resections (42.9% engraftment rate).
- PDX models demonstrated high similarity to patient tumors in morphology and genetics, maintained across passages.
- Drug sensitivity testing showed concordance between a PDX model and its patient, with one model reflecting patient insensitivity and another reflecting sensitivity to Pirarubicin and Cisplatin.
Conclusions:
- The developed panel of osteosarcoma PDX models accurately reflects the morphologic and genetic features of the original tumors.
- These PDX models serve as reliable preclinical tools for evaluating novel therapeutic strategies in osteosarcoma.
