Document Type
Article
Publication Date
2-1-2023
Original Citation
Yun J,
Heo W,
Lee E,
Na D,
Kang W,
Kang J,
Chae J,
Lee D,
Lee W,
Hwang J,
Yoo T,
Hong B,
Son H,
Noh D,
Lee C,
Moon H,
Kim J.
An integrative approach for exploring the nature of fibroepithelial neoplasms. Br J Cancer. 2023;128(4):626-37.
Keywords
JGM, Humans, Animals, Mice, Female, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Imatinib Mesylate, Breast Neoplasms, Phyllodes Tumor, Neoplasms, Fibroepithelial, Xenograft Model Antitumor Assays, Mammals
JAX Source
Br J Cancer. 2023;128(4):626-37.
ISSN
1532-1827
PMID
36522480
DOI
https://doi.org/10.1038/s41416-022-02064-2
Grant
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant nos. 2019R1A2C2005277, 2020R1A6A1A03047972, 2018R1D1A1B07045381), and by a grant from the Korea Health Industry Development Institute (KHIDI) (Grant nos. HI22C0497, HA15C0011) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (Grant no. HI14C1277) funded by the Ministry of Health and Welfare, Republic of Korea. CL was a distinguished Ewha Womans University Professor supported in part by the Ewha Womans University Research grant of 2018-2019. This study was supported in part by operational funds from The First Affiliated Hospital of Xi’an Jiaotong University.
Abstract
BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT.
METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT.
RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects.
CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT.
Comments
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