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

Autor: Juha Kononen, Nina Rintanen, Rami Mäkelä, Ville Härmä, Juha Rantala, Antti Arjonen, Teijo Kuopio
Rok vydání: 2020
Předmět:
Zdroj: Lung Cancer. 145:27-32
ISSN: 0169-5002
DOI: 10.1016/j.lungcan.2020.04.036
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: