title: 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.
authors.affiliation: Department of Head and Neck Surgery, University Hospital, Amiens, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Donnadieu
authors.affiliation: Department of Medical Oncology, University Hospital, Amiens, France.
authors.forename: Emma
authors.initials: E
authors.lastname: Lachaier
authors.affiliation: Department of Head and Neck Surgery, University Hospital, Amiens, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Peria
authors.affiliation: Department of Biochemistry, University Hospital, Amiens, France.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Saidak
authors.affiliation: Department of Maxillofacial Surgery, University Hospital, Amiens, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dakpe
authors.affiliation: Department of Pathology, University Hospital, Amiens, France.
authors.forename: Jean-Fortune
authors.initials: JF
authors.lastname: Ikoli
authors.affiliation: Department of Medical Oncology, University Hospital, Amiens, France.|EA4666, Université de Picardie-Jules Verne (UPJV), Amiens, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
authors.affiliation: Department of Head and Neck Surgery, University Hospital, Amiens, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Page
authors.affiliation: 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.
authors.forename: Antoine
authors.initials: A
authors.lastname: Galmiche
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D000068818:Cetuximab / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D048369:MAP Kinase Kinase 1 / Q000096:biosynthesis; D048748:MAP Kinase Kinase Kinase 3 / Q000096:biosynthesis; D058990:Molecular Targeted Therapy; D010766:Phosphorylation; D057285:Precision Medicine; D019908:Proto-Oncogene Proteins c-raf / Q000096:biosynthesis; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D019394:Ki-67 Antigen; D019908:Proto-Oncogene Proteins c-raf; D048748:MAP Kinase Kinase Kinase 3; D048369:MAP Kinase Kinase 1; D000068818:Cetuximab
keywords: Head and neck squamous cell carcinoma; Short-term culture of tumour fragments; Targeted therapies; Treatment personalization