title: Efficacy of cetuximab and panitumumab in oral squamous cell carcinoma cell lines: prognostic value of MAGE-A subgroups for treatment success.
abstract: BACKGROUND
  Over-expression of epidermal growth factor receptor (EGFR) has been observed in a variety of epithelial tumours. The selective inhibition of the associated signalling pathway using monoclonal antibodies appears to be a promising therapeutic target. Individual differences in response rates, particularly against highly selective chemotherapeutic agents, underline the need for further research of the molecular basis of this process. Previously described resistance mechanisms are not able to explain all refractory responses. Several subgroups of the melanoma-associated antigens (MAGE) tumour antigens were described in connection with regulatory functions relating to the cell cycle and chemosensitivity.
  
  
  METHODS
  In the present study, five cell lines of human squamous cell carcinomas were treated with cetuximab and panitumumab (0.01-100 μg/ml) over a period of 24 or 48 h. The efficacy of the agents used was measured dynamically using real-time cell analysis (RTCA). Subsequently, the expression levels of MAGE-A1, -A5, -A8, -A9, -A11 and -A12 were determined by RT-qPCR. A correlation between chemosensitivity and MAGE-A expression was investigated.
  
  
  RESULTS
  The tumour cell lines exhibited a very low overall response to the chemotherapy drugs. Only one cell line showed a cytostatic effect after treatment with cetuximab and panitumumab. This effect, however, was significant only for panitumumab. The expression of MAGE-A12 was significantly associated with greater efficacy of panitumumab. The expression of MAGE-A5 and -A8 was associated with poorer response rates after panitumumab treatment. Due to an insignificant effect of cetuximab on the number of viable cells, no correlation with the MAGE-A levels was observed.
  
  
  CONCLUSIONS
  For the first time, these results show a correlation between the efficacies of EGFR inhibitors and various MAGE-A subgroups in the treatment of HNSCC. Determining the MAGE-A status could help to improve the success of anti-tumour drug therapy. In addition, evaluating MAGE-A levels might be an important tool in the development of patient-specific treatment protocols.
authors: Department of Oral and Maxillofacial Plastic Surgery (Head: Alexander C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany. Electronic address: hartmann_s2@klinik.uni-wuerzburg.de.
authors: Stefan
authors: S
authors: Hartmann
authors: Ulrike
authors: U
authors: Kriegebaum
authors: Nora
authors: N
authors: Küchler
authors: Grit
authors: G
authors: Lessner
authors: Roman C
authors: RC
authors: Brands
authors: Christian
authors: C
authors: Linz
authors: Tim
authors: T
authors: Schneider
authors: Alexander C
authors: AC
authors: Kübler
authors: Urs D A
authors: UD
authors: Müller-Richter
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D020869:Gene Expression Profiling; D006801:Humans; D058950:Melanoma-Specific Antigens / Q000032:analysis*; D009062:Mouth Neoplasms / Q000188:drug therapy*; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D000077544:Panitumumab; D010446:Peptide Fragments / Q000032:analysis; D011379:Prognosis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C072011:MAGEA1 protein, human; C110882:MAGEA11 protein, human; C409589:MAGEA12 protein, human; C520253:MAGEA9 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Cetuximab; EGFR; MAGE-A; Panitumumab; Tumour antigen