Antikörper-Wirkstoff-Konjugate (ADCs) in der Therapie des Mammakarzinoms

Antibody-drug conjugates (ADC) combine the benefits of highly potent cytostatic therapy with the selective effect of targeted therapy. They consist of three components: a monoclonal antibody, a linker and a cytotoxic drug (payload). The antibody recognizes specific target structures on cancer cells enabling direct delivery of the drug. The linker enables the selective release of the drug within the target cell and beyond (bystander effect). All three components play an important role in the efficacy and tolerability of ADCs. Side effects are classified into on-target and off-target toxicities, with the desired bystander effect playing a crucial role in the treatment of heterogeneous tumor biology. In the early therapy setting, only trastuzumab emtansine (T-DM1) is currently approved, while the efficacy of sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) is being evaluated in phase III trials. In advanced stages, all three drugs have a proven efficacy. Studies are currently underway for datopotamab deruxtecan (Dato-DXd) in both early and advanced therapy situations, with promising initial results. This article provides an overview of the mechanism of action, practical applications, challenges, and potential future developments.