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

Autor: Donnadieu J; Department of Head and Neck Surgery, University Hospital, Amiens, France., Lachaier E; Department of Medical Oncology, University Hospital, Amiens, France., Peria M; Department of Head and Neck Surgery, University Hospital, Amiens, France., Saidak Z; Department of Biochemistry, University Hospital, Amiens, France., Dakpe S; Department of Maxillofacial Surgery, University Hospital, Amiens, France., Ikoli JF; Department of Pathology, University Hospital, Amiens, France., Chauffert B; Department of Medical Oncology, University Hospital, Amiens, France.; EA4666, Université de Picardie-Jules Verne (UPJV), Amiens, France., Page C; Department of Head and Neck Surgery, University Hospital, Amiens, France., Galmiche A; Department of Biochemistry, University Hospital, Amiens, France. galmiche.antoine@chu-amiens.fr.; EA4666, Université de Picardie-Jules Verne (UPJV), Amiens, France. galmiche.antoine@chu-amiens.fr.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2016 Apr 16; Vol. 16, pp. 273. Date of Electronic Publication: 2016 Apr 16.
DOI: 10.1186/s12885-016-2318-x
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: