Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor.

ABSTRACT: Cadherin 17 (CDH17) has emerged as a promising target for gastrointestinal (GI) cancers, which are often complicated by multidrug resistance (MDR) and recurrence. In this study, we developed 7MW4911, a CDH17-targeted antibody-drug conjugate (ADC) that incorporates a topoisomerase inhibitor MF-6 (Topi MF-6) payload linked via a cleavable linker, designed specifically to address MDR in GI cancers. 7MW4911 exhibited high specificity for CDH17-expressing cancer cells and potent cytotoxicity in vitro. In preclinical models, including patient-derived xenografts (PDXs) with distinct mutations, 7MW4911 achieved tumor growth inhibition ranging from 71% to 99%. Remarkably, 7MW4911 outperformed monomethyl auristatin E (MMAE)-based and Deruxtecan (DXd)-based ADCs in MDR models, highlighting its effect

SUBMITTER: Wang R 

PROVIDER: S-EPMC12281427 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature