Antti Arjonen1, Rami Mäkelä2, Ville Härmä3, Nina Rintanen4, Teijo Kuopio5, Juha Kononen6, Juha K Rantala7. 1. Misvik Biology Oy, Turku, Finland. Electronic address: arjonen@misvik.com. 2. Misvik Biology Oy, Turku, Finland. Electronic address: makela@misvik.com. 3. Misvik Biology Oy, Turku, Finland; University of Sheffield, Sheffield, UK. Electronic address: harma@misvik.com. 4. Jyväskylä Medical Centre, Jyväskylä, Finland. 5. Jyväskylä Medical Centre, Jyväskylä, Finland. Electronic address: teijo.kuopio@ksshp.fi. 6. Jyväskylä Medical Centre, Jyväskylä, Finland; Docrates Cancer Center, Helsinki, Finland. Electronic address: juha.kononen@docrates.com. 7. Misvik Biology Oy, Turku, Finland; University of Sheffield, Sheffield, UK. Electronic address: rantala@misvik.com.
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.
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.
Authors: Rami Mäkelä; Antti Arjonen; Ville Härmä; Nina Rintanen; Lauri Paasonen; Tobias Paprotka; Kerstin Rönsch; Teijo Kuopio; Juha Kononen; Juha K Rantala Journal: BMC Cancer Date: 2020-06-23 Impact factor: 4.430
Authors: Rami Mäkelä; Antti Arjonen; Aldwin Suryo Rahmanto; Ville Härmä; Janne Lehtiö; Teijo Kuopio; Thomas Helleday; Olle Sangfelt; Juha Kononen; Juha K Rantala Journal: Neoplasia Date: 2020-07-06 Impact factor: 5.715