NECTIN4-targeted antibody-drug conjugate is a potential therapeutic option for extramammary Paget disease

Area of Science:

• Oncology
• Dermatology
• Molecular Biology

Background:

• Extramammary Paget disease (EMPD) is a rare skin malignancy with limited treatment options for advanced stages.
• Nectin cell adhesion molecule 4 (NECTIN4) is implicated in various cancers and presents a potential therapeutic target.
• The role of NECTIN4 in EMPD and the efficacy of targeting it remain largely unexplored.

Purpose of the Study:

• To investigate NECTIN4 as a potential therapeutic target for EMPD.
• To evaluate the expression of NECTIN4 in EMPD tissues.
• To assess the impact of NECTIN4 inhibition and targeted therapy on EMPD cells.

Main Methods:

• Immunohistochemical analysis of NECTIN4 expression in 118 primary and 21 metastatic EMPD lesions.
• In vitro studies using an EMPD cell line (KS-EMPD-1) to assess NECTIN4 knockdown effects on proliferation and migration.
• Evaluation of the cytotoxic effects of a NECTIN4-targeted antibody-drug conjugate (ADC) on EMPD cell viability.

Main Results:

• NECTIN4 was expressed in both primary and metastatic EMPD lesions.
• NECTIN4 expression levels (H-score) were significantly higher in metastatic lesions compared to primary lesions.
• NECTIN4 knockdown inhibited EMPD cell proliferation and migration; NECTIN4-targeted ADC significantly reduced EMPD cell viability.

Conclusions:

• NECTIN4 is expressed in EMPD and its elevated expression in metastatic lesions suggests a role in disease progression.
• Targeting NECTIN4 through inhibition or ADC demonstrates significant anti-cancer effects in vitro.
• NECTIN4 represents a promising therapeutic target, and NECTIN4-targeted ADCs offer a potential treatment strategy for EMPD.