Application of a patient-derived xenograft model in cytolytic viral activation therapy for nasopharyngeal carcinoma

作者：Hsu Cheng Lung^*; Kuo Yung Chia; Huang Yenlin; Huang Yin Cheng; Lui Kar Wai; Chang Kai Ping; Lin Tung Liang; Fan Hsien Chi; Lin An Chi; Hsieh Chia Hsun; Lee Li Yu; Wang Hung Ming; Li Hsin Pai; Chang Yu Sun

来源：Oncotarget, 2015, 6(31): 31323-31334.

DOI：10.18632/oncotarget.5544

• NPC
• PDX
• EBV
• target therapy
• viral lytic therapy

Nasopharyngeal carcinoma (NPC) is an Epstein Barr virus (EBV)-related malignancy in which the tumor microenvironment plays a pivotal role in tumor progression. Here, we developed two patient-derived xenograft (PDX) mouse lines from engrafted NPC metastatic tumors. Positive staining for EBV-encoded small RNAs confirmed that these tumors harbored EBV, and gene expression profile analyses further showed that the PDX was highly similar to the primary parent tumor. In vivo drug screening using the PDX system demonstrated that gemcitabine had the best antitumor effect among the tested drugs. The donor of this PDX also showed excellent responsiveness to gemcitabine treatment. The combination of gemcitabine and valproic acid exerted synergistic antitumor effects. Further addition of ganciclovir to this two-drug combination regimen enhanced cytolytic viral activation, yielding the best antitumor response among tested regimens. Treatment with this three-drug combination regimen decreased plasma EBV-DNA load, tumor viral concentration, and the number of viable tumor cells to a greater extent than the two-drug gemcitabine and valproic acid combination. These results highlight the value of PDX models in the development of EBV-targeted strategies to treat NPC.

• 单位
  长春大学