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Image-based ex vivo drug screen to assess targeted therapies in recurrent thymoma
Antti Arjonen1, Rami Mäkelä1, Ville Härmä2
1Misvik Biology Oy, Turku, Finland.
Objectives:
Thymoma is a rare malignancy derived from the thymic epithelial cells. No standard salvage treatments are available for recurrent thymoma and due to the low number of cases, alternative treatment regimens have been assessed only in small case series with varying success. The aim of this study was to use an image-based ex vivo drug screening strategy to assess efficacy of a large panel of anti-cancer agents for thymoma using patient derived tumor cells.
Materials And Methods:
Vital tumor and tumor associated cells were used to assess the efficacy of 147 anti-cancer drugs including approved and experimental agents. Drug efficacy was analyzed at single cell resolution using image-based high content drug screening to assess tumor cell specific responses. Molecular profiling and histopathology was used to confirm the drug targets identified by the screen.
Results:
The ex vivo drug screen identified selective sensitivity of the cancerous epithelial thymoma cells to EGFR-, HDAC- and mTOR-inhibition. Histopathology confirmed high protein level expression of EGFR in the patient's tumor. Patient was initiated treatment with Cetuximab resulting in stable disease after relapse on five different chemotherapy regimens.
Conclusion:
The results show that the image-based ex vivo therapy efficacy screening strategy can be used to identify patient and tumor relevant drug sensitivity patterns in thymoma. The results also warrant continued research on EGFR as a biomarker and therapy target in recurrent thymomas.
Insights
This study used ex vivo drug screening to identify effective treatments for recurrent thymoma. Cetuximab, targeting EGFR, showed promise in a patient resistant to chemotherapy, highlighting EGFR as a potential therapeutic target.
Area of Science:
- Oncology
- Translational Medicine
Background:
- Thymoma is a rare epithelial malignancy with limited salvage treatment options for recurrent cases.
- Small case series have shown variable success with alternative treatment regimens.
- Developing effective therapies for recurrent thymoma is challenging due to its rarity.
Purpose of the Study:
- To employ an image-based ex vivo drug screening strategy to evaluate a broad range of anti-cancer agents.
- To assess the efficacy of these agents on patient-derived thymoma cells.
- To identify potential targeted therapies for recurrent thymoma.
Main Methods:
- Utilized vital tumor and associated cells for drug efficacy assessment.
- Screened 147 anti-cancer drugs (approved and experimental) using image-based high-content screening at single-cell resolution.
- Confirmed drug targets through molecular profiling and histopathology.
Main Results:
- Identified selective sensitivity of thymoma cells to EGFR, HDAC, and mTOR inhibitors.
- Histopathology confirmed high EGFR protein expression in the patient's tumor.
- Patient treated with Cetuximab achieved stable disease after failing five prior chemotherapy regimens.
Conclusions:
- Image-based ex vivo drug screening effectively identifies patient- and tumor-specific drug sensitivities in thymoma.
- EGFR warrants further investigation as a predictive biomarker and therapeutic target in recurrent thymomas.
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