Antitumor effect and enhancement of cytotoxic drug activity by cetuximab in nasopharyngeal carcinoma cells.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in southern China and South East Asia. Epidermal growth factor receptor (EGFR) has been proposed as a new target for anticancer therapy. EGFR was over-expressed in 85% of NPC tissues and was associated with poor prognosis.


METHODS
EGFR protein expression in four NPC cell lines, CNE-2, HONE-1, HK1 and C666-1, was examined by Western immunoblotting. The antitumor effect of cetuximab was studied in the cell lines, either alone or in combination with cisplatin or paclitaxel.


RESULTS
EGFR protein expression was highest in the HK1 cell line, moderate in CNE-2 and HONE-1, and lowest in C666-1. Single agent cetuximab demonstrated significant antitumor effect in the HK1 and HONE-1 cell lines, but minimal activity in CNE-2 and C666-1 cells. When cetuximab was combined with cisplatin or paclitaxel in the HK1 and HONE-1 cell lines, an additive enhancement of cytotoxic drug activity was demonstrated.


CONCLUSIONS
Cetuximab demonstrated single agent activity selectively in NPC cell lines with moderate to high EGFR protein expression. Cetuximab could also additively enhance the antitumor effects of cisplatin or paclitaxel in these NPC cell lines. These results support the rationale of combining cetuximab with current standard chemotherapy to further improve the therapeutic ratio in the treatment of NPC. Future studies should aim at defining the predictive markers for response to cetuximab in order to select the responsive tumor for the correctly targeted agents.
Sung
Fion Lan
FL
Department of Clinical Oncology, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong.
Poon
Terence Cheun Wai
TC
Hui
Edwin Pun
EP
Ma
Brigette Buig Yue
BB
Liong
Eleanore
E
To
Ka Fai
KF
Huang
Dolly Poon Wai Sin
DP
Chan
Anthony Tak Cheung
AT
D000911:Antibodies, Monoclonal / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000633:toxicity*; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D000068818:Cetuximab; D002945:Cisplatin / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000633:toxicity; D011379:Prognosis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D066246:ErbB Receptors; D017239:Paclitaxel; D000068818:Cetuximab; D002945:Cisplatin