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.
Subject(s)
Carcinoma, Squamous Cell/drug therapy , Cell Culture Techniques , Cell Proliferation/drug effects , Head and Neck Neoplasms/drug therapy , Molecular Targeted Therapy , Apoptosis/drug effects , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Cetuximab/administration & dosage , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , Ki-67 Antigen/biosynthesis , MAP Kinase Kinase 1/biosynthesis , MAP Kinase Kinase Kinase 3/biosynthesis , Phosphorylation , Precision Medicine , Proto-Oncogene Proteins c-raf/biosynthesis , Squamous Cell Carcinoma of Head and NeckABSTRACT
BACKGROUND: Cetuximab is a targeted therapy with demonstrated efficacy in the management of head and neck squamous cell carcinoma (HNSCC). However, no laboratory assay is available to predict its efficacy in an individual patient. METHODS: Short-term cultures of tumor slices were performed on 9 tumor samples obtained after surgical resection in patients. Cancer cell proliferation was evaluated by immunohistochemistry and the impact of cetuximab on cell proliferation was examined. RESULTS: Tumor architecture and the heterogeneous composition of HNSCC were preserved for at least 48 hours during short-term culture of tumor slices. HNSCC cells demonstrated a heterogeneous individual response to cetuximab. CONCLUSION: Short-term culture of tumor slices is a strategy to estimate the clinical activity of cetuximab in individual patients with HNSCC. Further studies are required to correlate the results obtained with the clinical response of individual patients to cetuximab. © 2015 Wiley Periodicals, Inc. Head Neck 38: E911-E915, 2016.