Here, we have explored the essential role of DNA repair in AST-3424-mediated pharmacological activities in vitro and in vivo….To further examine the essential role of DNA repair in AST-3424 anti-tumor activity, we utilized two PDX models with BRCA deleterious mutations lacking capacity of double-strand DNA repair. The results showed that AST-3424 exhibited excellent anti-tumor activity in two pancreatic PDX models with BRCA deleterious mutations and high expression of AKR1C3....DNA repair plays an essential role in AST-3424-mediated in vitro biological activities and in vivo anti-tumor activity.