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Updated: Sep 1, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Establishment of an epithelioid sarcoma PDCs and PDX to evaluate drug sensitivity
Weifang Wang1, Xiuhao Zhao2, Ruirong Yi3
1Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Abstract:
Epithelioid sarcoma (ES) is a very rare mesenchymal malignancy. Its oncogenesis remains unknown, and few therapies are available for advanced patients. Improved therapies, such as combined therapies, are urgently needed for the treatment of advanced ES. To identify precision drugs for advanced ES patients, the sensitivity of the drugs must be screened and evaluated before they are used for treatment. In the present study, tumour tissue from an ES patient was subjected to NGS sequencing, cell culture and the construction of a PDX model. Using the early generations of tumour-derived cells, we performed a screen and found that the combined drugs ADM and trametinib exhibited coefficiency in tumour inhibition. This conclusion was further confirmed in experiments with later generations of cells and PDX models. Therefore, we suggest that early generations of tumour-derived cells be used to test the sensitivity of ES tumours to candidate drugs. Moreover, we speculate that trametinib may be combined with chemotherapy in ES patients to prolong the duration of the chemotherapeutic response.
Insights
Epithelioid sarcoma (ES) drug sensitivity can be predicted using early-generation tumor cells. Combined doxorubicin (ADM) and trametinib show efficacy in inhibiting ES tumor growth.
Area of Science:
- Oncology
- Medical Research
- Cancer Therapeutics
Background:
- Epithelioid sarcoma (ES) is a rare mesenchymal malignancy with unknown oncogenesis.
- Limited therapeutic options exist for advanced ES patients, necessitating improved treatment strategies.
- Precision medicine approaches require pre-treatment drug sensitivity screening.
Purpose of the Study:
- To identify effective precision drugs for advanced epithelioid sarcoma.
- To evaluate the drug sensitivity of ES tumors using early-generation cells.
- To explore combination therapies for enhanced tumor inhibition.
Main Methods:
- Next-generation sequencing (NGS) of patient tumor tissue.
- Establishment of cell cultures and patient-derived xenograft (PDX) models.
- Drug sensitivity screening using early-generation tumor-derived cells.
Main Results:
- Combined doxorubicin (ADM) and trametinib demonstrated synergistic tumor inhibition.
- Efficacy of the combined drug regimen was confirmed in later cell generations and PDX models.
- Early-generation tumor-derived cells accurately predicted drug sensitivity.
Conclusions:
- Utilizing early-generation tumor-derived cells is a viable method for ES drug sensitivity testing.
- The combination of ADM and trametinib shows promise for treating advanced epithelioid sarcoma.
- Trametinib may enhance chemotherapy response duration in ES patients.
