AI Article Synopsis
- Nasopharyngeal carcinoma (NPC) is linked to the Epstein Barr virus, and the tumor's environment greatly influences its growth and metastasis.
- Researchers created patient-derived xenograft (PDX) mouse models from NPC tumors, confirming the presence of EBV and the models closely reflected the original tumors' characteristics.
- In drug testing, gemcitabine proved the most effective treatment, and its combination with valproic acid and ganciclovir showed enhanced antitumor effects, significantly reducing EBV levels and viable tumor cells compared to the two-drug regimen.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741608 | PMC |
| http://dx.doi.org/10.18632/oncotarget.5544 | DOI Listing |
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