Elsevier

Lung Cancer

Volume 145, July 2020, Pages 27-32
Lung Cancer

Image-based ex vivo drug screen to assess targeted therapies in recurrent thymoma

https://doi.org/10.1016/j.lungcan.2020.04.036Get rights and content
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open access

Highlights

  • Ex vivo assessment of drug efficacy in recurrent thymoma.

  • Image-based drug screening assay for cell type stratified dose response profiling.

  • EGFR-TKIs identified as therapy option in EGFR expressing thymoma.

  • Cetuximab used as a targeted therapy to treat metastatic thymoma following 5th recurrence.

Abstract

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.

Abbreviations

EGFR
Epidermal Growth Factor Receptor
GR
Growth Rate
NGS
Next Generation Sequencing
TET
Thymic Epithelial Tumor
TKI
tyrosine kinase inhibitor

Keywords

Thymoma
Personalized medicine
Ex vivodrug screening
Targeted therapy
EGFR

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1

Both authors contributed equally to this work.