Enhanced Enhertu-Resistant HER2-Positive Breast Cancer Models for ADC Resistance Research

Acquired resistance to HER2-targeted antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (Enhertu), significantly limits durable clinical benefit in HER2-positive breast cancer. GemPharmatech has established robust Enhertu-resistant models using the HER2-positive JIMT-1 xenograft system through repeated drug exposure. This includes a resistant cell line (JIMT-1-Enhertu-R) and a more stringent in vivo-selected model (JIMT-1-Enhertu-ER). Both models retained high HER2 expression while exhibiting marked resistance to the DXd payload, associated with upregulation of drug efflux transporters including ABCG2. These well-characterized models provide valuable platforms for elucidating ADC resistance mechanisms and evaluating next-generation HER2-targeted therapies.