Malignant Phyllodes Tumors

An integrative approach for exploring the nature of fibroepithelial neoplasms

It took many years to get this published :)

We were able to establish patient-derived xenograft models from patients with a rare type of breast malignancy which is the malignant phyllodes tumor, and to our knowledge, ours are the first PDX models for this tumor.

I especially applaud to the hard works of Dr. Yun and Dr. Heo.

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.

An integrative approach for exploring the nature of fibroepithelial neoplasms.

Yun J, Heo W, Lee ES, Na D, Kang W, Kang J, Chae J, Lee D, Lee W, Hwang J, Yoo TK, Hong BS, Son HY, Noh DY, Lee C, Moon HG, Kim JI.

Br J Cancer. 2022 Dec 16. doi: 10.1038/s41416-022-02064-2.