A multicenter study on TROP2 as a potential targeted therapy for extramammary Paget disease in Japan

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy treatments for metastatic or unresectable EMPD remains poor, development novel therapeutic approach strongly desired. However, lack models has hampered investigation EMPD. Here we investigated whether trophoblast cell surface antigen 2 (TROP2) could be promising target We retrospectively collected 108 samples from 54 patients with primary and 10 Japanese institutions, compared TROP2 expression between lesions each paired sample. In vitro assays were performed using newly established line, KS-EMPD-1. was homogeneously expressed patient tissues, regardless lesions. The KS-EMPD-1 cells treated TROP2-targeted antibody–drug conjugate (ADC), sacituzumab govitecan, it significantly reduced viability dose-dependent manner alone. Knockdown migration, caused slight upregulation apoptosis-related factors, together downregulation epithelial-to-mesenchymal transition-related factors. These findings suggest ADC may treatment option

Language: Английский

TROP2 Expression and Therapeutic Implications in Cutaneous Squamous Cell Carcinoma: Insights From Immunohistochemical and Functional Analysis

Experimental Dermatology, Journal Year: 2024, Volume and Issue: 33(10)

Published: Oct. 1, 2024

ABSTRACT Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer, but treatments for advanced cases have limited efficacy. Trophoblast cell‐surface antigen 2 (TROP2) protein that widely expressed in various tumours, where it exerts significant influence over critical processes such as tumour growth, apoptosis, migration, invasion and metastasis. Sacituzumab govitecan, an antibody‐drug conjugate (ADC) targeting TROP2, emerging promising strategy anticancer therapy. In this study, we investigated TROP2 expression cSCC tissues from 51 patients evaluated its function the A431 human SCC line. Immunohistochemical analysis revealed on plasma membrane cells. cells showed sensitivity to sacituzumab govitecan with concentration‐dependent decrease viable number. addition, Knockdown resulted decreased cyclin D1 BCL‐2, along reduced viability. also vimentin, migratory capacity. These findings suggest plays crucial role proliferation highlight potential therapeutic option cSCC.

Language: Английский