51P The PRMT1-LDHA-Lactate positive feedback loop mediates resistance to T-DXd in breast cancer

Trastuzumab deruxtecan (T-DXd) improves outcomes in HER2-positive breast cancer, but drug resistance limits long-term efficacy. Cuproptosis, a copper-dependent cell death mechanism, may counter resistance. Dysregulated lactate dehydrogenase A (LDHA) and protein arginine methyltransferase 1 (PRMT1) promote tumor progression, but their role in T-DXd resistance via cuproptosis regulation remains unclear. This study investigates the PRMT1-LDHA-lactate feedback loop in mediating resistance by inhibiting cuproptosis.