Establishment of a Patient-derived Xenograft for Development of Personalized HER2-targeting Therapy in Gastric Cancer

Anticancer Res. 2018 Jan;38(1):287-293. doi: 10.21873/anticanres.12220.

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 anti-cancer 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.

Keywords: Patient-derived xenograft; gastric cancer; human epidermal growth factor receptor 2; personalized treatment.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Aged
  • Animals
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Female
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Precision Medicine
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Trastuzumab / pharmacology
  • Trastuzumab / therapeutic use*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Immunological
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab