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Short-term culture of tumour slices reveals the heterogeneous sensitivity of human head and neck squamous cell carcinoma to targeted therapies

Abstract : Background: Despite recent progress, investigating the impact of targeted therapies on Head and Neck Squamous Cell Carcinoma (HNSCC) remains a challenge. We investigated whether short-term culture of tumour fragments would permit the evaluation of tumour sensitivity to targeted therapies at the individual level. Methods: We cultivated tumour slices prepared from 18 HNSCC tumour samples obtained during surgical resection. The samples were treated for 48 h with a panel of 8 targeted therapies directed against selected oncogenic transduction pathways. We analysed the cell proliferation index (CPI) of tumour cells using Ki67 labelling and the activation status of the RAF-MEK-ERK cascade through ERK phosphorylation analysis. Results: Fourteen tumours were successfully analysed after short-term culture of tumour samples, revealing a striking individual heterogeneity of HNSCC in terms of tumour cell sensitivity to targeted therapies. Using 50 % inhibition of CPI as threshold, sorafenib was shown to be active in 5/14 tumours. Cetuximab, the only approved targeted drug against HNSCC, was active in only 2/14 tumours. A more than 50 % inhibition was observed with at least one drug out of the eight tested in 10/14 tumours. Cluster analysis was carried out in order to examine the effect of the drugs on cell proliferation and the RAF-MEK-ERK cascade. Conclusions: In vitro culture of tumour fragments allows for the evaluation of the effects of targeted therapies on freshly resected human tumours, and might be of value as a possible guide for the design of clinical trials and for the personalization of the medical treatment of HNSCC.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03593495
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Soumis le : mercredi 2 mars 2022 - 09:27:08
Dernière modification le : mercredi 27 avril 2022 - 04:03:03

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Jerome Donnadieu, Emma Lachaier, Marine Peria, Zuzana Saidak, Stephanie Dakpe, et al.. Short-term culture of tumour slices reveals the heterogeneous sensitivity of human head and neck squamous cell carcinoma to targeted therapies. BMC CANCER, 2016, 16, ⟨10.1186/s12885-016-2318-x⟩. ⟨hal-03593495⟩

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