Establishment of a patient-derived xenograft for development of personalized HER2-targeting therapy in gastric cancer

Abstract

Background/Aim: To maximize success rate for development of HER2-targeted therapeutics, patient-derived xenograft (PDX) models reflecting HER2-positive gastric cancer (HER2+ GC) patients were established. Materials and Methods: GC tissues obtained from surgery of GC patients were implanted into immune-deficient mice, and tumor tissue of HER2+ PDXs were verified of the patient-mimic HER2 expression by immunohistochemistry and explored for the feasibility by testing with Herceptin, the approved therapeutics and novel HER2 antibody therapeutics being developed. Results: We obtained 5 cases of HER2+ GC PDX models reflecting patient’s GC tumor, consisting of 2 cases of HER2 3+ and 2 cases of HER2 2+. Novel HER2 antibody displayed significantly improved anticancer efficacy in combination with Herceptin. Conclusion: The HER2+ GC PDX models were successfully established to be utilized for preclinical evaluation of HER2-targeting drugs and combined therapies for GC treatment, as an ideal platform of personalized tools for precision therapy.