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Updated: Sep 6, 2025
Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
Published on: June 13, 2019
A Multicentre Clinical Study of Sarcoma Personalised Treatment Using Patient-Derived Tumour Xenografts
Aims:
Medication for advanced sarcomas has not improved for three decades. Patient-derived tumour xenografts (PDTX) are a promising solution for developing new therapies and real-time personalised medicine because of their highly effective prediction of drug efficacy. However, there is a dearth of PDTX models for sarcomas due to the scarcity and heterogeneity of the disease.
Materials And Methods:
A multicentre clinical collaborative study (ChiCTR-OOC-17013617) was carried out. Fresh patient tumour tissues via resection or biopsy were used for the PDTX set-up. The standard medical care chosen by the physician was given to the patient, in parallel with testing on multiple regimens. The outcomes of patients' responses and PDTX tests were compared. Comprehensive analyses were carried out to assess the clinical value of PDTX for the treatment of sarcomas. Living tissues from successfully engrafted cases were deposited into a repository.
Results:
Forty-two cases, including 36 bone sarcomas and six soft-tissue sarcomas, were enrolled; the overall engraftment rate was 73.8%. Histopathological examination showed a 100% consistency between primary tumours and tumour grafts. The engraftment rate was independent of age, gender and sampling methods, but was associated with subtypes of tumour. The outgrowth time of tumour grafts could be associated with prognosis. Major somatic mutations in tumour grafts occurred primarily in common tumour driver genes. Poor prognosis was associated with the KMT2C mutation. A drug efficacy test showed complete concordance between the PDTX model and patients' responses in 17 regimens.
Conclusion:
PDTX is an ideal preclinical model for sarcomas because of its faithful preservation of the heterogeneity of the disease, a satisfactory engraftment rate and high accuracy in its prediction of drug efficacy.
Insights
Patient-derived tumor xenografts (PDTX) show high accuracy in predicting sarcoma drug efficacy. This preclinical model effectively preserves tumor heterogeneity, offering a promising solution for developing new sarcoma therapies.
Area of Science:
- Oncology
- Translational Medicine
- Cancer Research
Background:
- Advanced sarcoma treatment has seen no significant progress in 30 years.
- Patient-derived tumor xenografts (PDTX) are valuable for predicting drug efficacy and enabling personalized medicine.
- A lack of sarcoma PDTX models exists due to disease rarity and heterogeneity.
Purpose of the Study:
- To establish and evaluate patient-derived tumor xenografts (PDTX) for sarcoma treatment.
- To assess the clinical utility of PDTX models in predicting patient response to various drug regimens.
- To create a repository of living sarcoma PDTX models for future research.
Main Methods:
- A multicenter clinical study involved collecting fresh patient sarcoma tissues for PDTX development.
- Patients received standard medical care concurrently with parallel PDTX drug efficacy testing.
- Outcomes from patient responses and PDTX tests were compared for concordance.
Main Results:
- A 73.8% engraftment rate was achieved across 42 sarcoma cases (36 bone, 6 soft-tissue).
- 100% histopathological consistency was observed between primary tumors and their grafts.
- PDTX models demonstrated complete concordance with patient responses for 17 drug regimens, with KMT2C mutations linked to poor prognosis.
Conclusions:
- PDTX models are ideal preclinical tools for sarcomas, accurately reflecting disease heterogeneity.
- These models offer a satisfactory engraftment rate and high predictive accuracy for drug efficacy.
- PDTX development and validation pave the way for improved sarcoma therapeutics and personalized treatment strategies.
