A novel DXd-ADC technology has been discovered with the study of ADC linker technology applied to a potent DNA topoisomerase I inhibitor. A high drug-to-antibody ratio with homogeneous conjugation, has strong potency on heterogeneous tumors by the bystander antitumor effect, and alleviates safety concerns in systemic circulation with its high linker-drug stability. Trastuzumab deruxtecan (T-DXd) could provide valuable therapy with great potential for providing effective treatment for breast cancer and other HER2-expressing cancers in clinical settings. Indeed, T-DXd was recently approved for the treatment of patients with HER2-positive unresectable or recurrent breast cancers in the United States, Japan, and EU and with HER2-positive unresectable or recurrent gastric cancers in the United States and Japan.