シオミ　タツシ   Tatsushi Shiomi   塩見　達志    所属   川崎医科大学  医学部 臨床医学　病理学    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan.
掲載誌名	正式名：Scientific reports 略　 称：Sci Rep ISSNコード：20452322/20452322
掲載区分	国外
巻・号・頁	15(1),pp.409
著者・共著者	Takamichi Ito, Yuka Tanaka, Dai Ogata, Haruto Nishida, Tatsushi Shiomi, Ryo Tanaka, Aya Kawaguchi, Azusa Miyashita, Satoshi Fukushima, Naoko Shojiguchi, Hiroyuki Goto, Yaei Togawa, Takahiro Kiyohara, Yoshinao Oda, Takeshi Nakahara
発行年月	2025/01
概要	Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD models has hampered investigation of EMPD. Here we investigated whether trophoblast cell surface antigen 2 (TROP2) could be a promising therapeutic target for EMPD. We retrospectively collected 108 samples from 54 patients with primary and metastatic EMPD from 10 Japanese institutions, and compared TROP2 expression between primary and metastatic lesions of each paired sample. In vitro assays were performed using a newly established EMPD cell line, KS-EMPD-1. TROP2 was strongly and homogeneously expressed in patient tissues, regardless of primary or metastatic lesions. The KS-EMPD-1 cells were treated with a TROP2-targeted antibody-drug conjugate (ADC), sacituzumab govitecan, and it significantly reduced cell viability in a dose-dependent manner compared with that of the cells treated with sacituzumab alone. Knockdown of TROP2 reduced cell viability and cell migration, and caused slight upregulation of the apoptosis-related factors, together with downregulation of the epithelial-to-mesenchymal transition-related factors. These findings suggest that a TROP2-targeted ADC may be a promising treatment option for unresectable EMPD.
DOI	10.1038/s41598-024-84566-y
PMID	39747638