Extramammary Paget’s disease patient-derived xenografts harboring ERBB2 S310F mutation show sensitivity to HER2-targeted therapies

Takuya Maeda, Shinya Kitamura, Hiroshi Nishihara, Teruki Yanagi

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Although the prognosis of advanced extramammary Paget’s disease (EMPD) is poor, there have been no preclinical research models for the development of novel therapeutics. This study aims to establish a preclinical research model for EMPD. We transplanted EMPD tissue into immunodeficient NOD/Scid mice. Histopathological and genetic analyses using a comprehensive cancer panel were performed. For in vivo preclinical treatments, trastuzumab, lapatinib, docetaxel, or eribulin were administered to patient-derived xenograft (PDX) models. Tissue transplanted from the EMPD patient was enlarged in NOD/Scid mice and was transplanted into further generations. Both the transplantation of PDX into nu/nu mice and the reanimation of the cryopreserved xenografted tumors in NOD/Scid mice were successful. We also established an EMPD-PDX-derived primary cell culture. Histopathologically, the xenografted tumors were positive for CK7, which was consistent with the patient’s tumors. Genetically, the pathogenic mutation ERBB2 S310F was detected in the patient’s tumors (primary intraepidermal lesion, metastatic lymph node) and was observed in the xenografted tumors even after continued passages. The xenografted tumors responded well to trastuzumab and lapatinib therapy. Also, cytotoxic agents (docetaxel and eribulin) were effective against the xenografted tumors. This PDX model (EMPD-PDX-H1) could be a powerful tool for the research and development of EMPD treatments.

本文言語English
ページ(範囲)5867-5875
ページ数9
ジャーナルOncogene
39
36
DOI
出版ステータスPublished - 2020 9 3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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