Application of Omics and Targeted Anti-Cancer Therapy in Npc Pdx Model

Nasopharyngeal carcinoma (NPC) is a head and neck malignancy associated with Epstein-Barr virus (EBV) infection. So far human is the only natural host for EBV, thus EBV NPC animal model is not yet available. Patient derived xenograft (PDX) mouse model preserves the heterogeneous genetic make-up and biosignature of the patient’s tumor. Thus, it is a reliable platform for precision cancer therapeutic prediction and preclinical drug efficacy testing. We have established five nasopharyngeal carcinoma (NPC) PDX mouse model with the collaboration with the physicians of Chang Gung Memorial Hospital (CGMH). Whole-exome sequencing (WES) and copy number variations (CNVs) were analyzed. Relatively high incident rate of CNV aberration were detected. To evaluate the preclinical cancer drug efficacy and characterize the possible mechanism of these drug, this proposal aims to apply each NPC PDX model to perform (1) genomic analysis; (2) preclinical drug response trial; (3) transcriptomic analyses (RNA-seq) before and after drug treatment; and (4) proteome analyses before and after drug treatment. To understand how EBV may play a role in mediating CNV or chromosomal instability in NPC, an EBV endonuclease BALF3 involved in virus packaging will be overexpressed in NPC cells. The chromosomal CNV of these cells will be examined and characterized in order to reveal the molecular mechanism by which EBV promotes NPC tumor progression.

Project ID:PC10707-0067
External Project ID:MOST107-2320-B182-003