Washington University researchers described an in vivo “antibody–ADC click” approach designed to overcome antibody-drug conjugate resistance driven by heterogeneous or low target expression. Using trans-cyclooctene and tetrazine chemistry, the strategy assembles a higher-order dual-targeting ADC complex inside the body after sequential dosing. In mouse models across pancreatic, gastric and breast cancer, the clicked constructs accumulated more efficiently in tumors and slowed or halted progression, including in tumors where HER2 expression is low, ultralow or mismatched with conventional ADC targeting. The work aims to make ADC behavior less dependent on a single antigen presentation profile. Complementing this platform concept, another group reported how disabling tumor DNA repair pathways could sensitize cancers to genotoxic therapy, adding a separate axis for turning tumor resilience into a tractable vulnerability.