An integrative approach for exploring the nature of fibroepithelial neoplasms.

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.

• Authors: Jihui Yun, Woohang Heo, Eun-Shin Lee, Deukchae Na, Wonyoung Kang, Jinjoo Kang, Jeesoo Chae, Dakyung Lee, Woochan Lee, Jinha Hwang, Tae-Kyung Yoo, Bok Sil Hong, Hye-Youn Son, Dong-Young Noh, Charles Lee, Hyeong-Gon Moon, Jong-Il Kim
• Journal: British journal of cancer (Br J Cancer) Vol. 128 Issue 4 Pg. 626-637 (02 2023) ISSN: 1532-1827 [Electronic] England
• PMID: 36522480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Phosphatidylinositol 3-Kinases
• Imatinib Mesylate

Topics

• Humans
• Animals
• Mice
• Female
• Phosphatidylinositol 3-Kinases
• Cell Line, Tumor
• Imatinib Mesylate
• Breast Neoplasms (pathology)
• Phyllodes Tumor (pathology)
• Neoplasms, Fibroepithelial
• Xenograft Model Antitumor Assays
• Mammals