Next generation of antibody–drug conjugates
Antibody–drug conjugate development in solid tumors is increasingly dominated by topoisomerase I inhibitor payloads, raising concerns about resistance and limited mechanistic diversity.
Deruxtecan illustrates how a previously discontinued cytotoxic agent can be reengineered into an effective antibody– drug conjugate payload through antibody-directed delivery.
Repurposing legacy small molecules, including antifolates and nucleoside analogs, may expand opportunities to diversify antibody–drug conjugate payload classes.
Mechanism-guided frameworks for payload selection may enable systematic evaluation of archived compounds for next-generation antibody–drug conjugate development.
https://www.cell.com/trends/cancer/fulltext/S2405-8033(26)00076-2
