Understanding ADC Resistance using Preclinical Enhertu-induced Resistant Models

Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies (mAbs) with potent cytotoxic payloads, offering a promising approach for targeted cancer therapy. Enhertu (trastuzumab deruxtecan, DS-8201), an ADC targeting HER2-positive cancers, has demonstrated remarkable efficacy in clinical settings, setting new benchmarks for anti-HER2 ADCs. However, drug resistance remains a significant challenge, underscoring the need to elucidate resistance mechanisms and develop strategies to overcome them. To address this important question, we established a robust preclinical platform to study Enhertu resistance by subjecting HER2-positive JIMT-1 xenograft tumors to a series of in vivo passaging and drug induction.