title: Markers of chemoradiation resistance in patients with locally advanced head and neck squamous cell carcinoma, treated by intra-arterial carboplatin and concurrent radiation.
abstract: The onset of chemo- and/or radio-resistance in tumour cells is one of the main causes of failure of integrated treatment protocols combining intra-arterial administration of platinum derivatives and radiotherapy, and is associated with recurrent disease and/or distant metastases. In the present study, the expression of a series of markers of chemo- and/or radio-resistance was investigated in 21 patients with advanced squamous cell carcinoma of the head and neck treated with combined intra-arterial carboplatin and radiotherapy. The results were correlated with local response to treatment, recurrence and overall and disease-free survival. In non-responders or in patients presenting recurrence, caspase 8 was significantly (p 0.05) under-expressed while p-Gp (p 0.035) and MDR-3 (p 0.049) were significantly over-expressed. Tumours with unfavourable outcome more frequently over-expressed two or more anti-apoptotic factors (p-53, BCL-2, BCL-x) (p 0.01). Patients with shorter overall survival, significantly overexpressed p53 (p 0.04), LRP (p 0.038) and a larger number of trans-membrane transport proteins compared with those who survived more than one year (p 0.013). Finally, patients with the shortest disease-free survival presented over-expression of p53 (p 0.027) and BCL-x (p 0.023). Further studies are necessary to confirm the possibility, in a future perspective, of using a panel of markers of chemo- and radio-resistance to identify those patients potentially sensitive to the treatment and to avoid patients at high risk of resistance from being submitted to ineffective and toxic treatment protocols.
authors.affiliation: Department of Otolaryngology HN Surgery, University of Pavia, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Mannarini
authors.forename: G
authors.initials: G
authors.lastname: Bertino
authors.forename: P
authors.initials: P
authors.lastname: Morbini
authors.forename: C
authors.initials: C
authors.lastname: Villa
authors.forename: M
authors.initials: M
authors.lastname: Benazzo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D051020:bcl-X Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D051020:bcl-X Protein; D016190:Carboplatin