49P EccDNA-LYL1 mediates T-DXd resistance by inducing RAB26-dependent lysosomal dysfunction and impairing cGAS-STING activation in HER2-positive breast cancer

Trastuzumab deruxtecan (T-DXd) is the standard second-line therapy for HER2-positive (HER2+) breast cancer (BC), yet resistance remains a critical challenge. Extrachromosomal circular DNA (eccDNA) drives tumor heterogeneity and drug resistance. This study investigates the role of eccDNA-LYL1 in T-DXd resistance and explores therapeutic strategies to reverse it.