An orthotopic model of metastatic nasopharyngeal carcinoma and its application in elucidating a therapeutic target that inhibits metastasis.

ABSTRACT

To define and therapeutically target mechanisms that mediate nasopharyngeal carcinoma (NPC) metastasis, we have developed a unique orthotopic xenograft mouse model that accurately recapitulates the invasive and metastatic behavior of human disease. Based on clinical and laboratory evidence that the PI3K/Akt/mTOR axis is involved in aggressive NPC tumor behavior, we chose it as a therapeutic target to test the utility of our orthotopic system for evaluating the effectiveness of a targeted treatment for metastatic NPC. Demonstrated herein, we have shown that both the development and growth of metastatic lesions are markedly reduced by the mTOR inhibitor sirolimus. Thus, this orthotopic model provides a platform to study potential therapeutics for advanced NPC and demonstrates that targeting the PI3K/Akt/mTOR pathway is a promising intervention against disseminated disease.