The aim of this study is to explore whether the lurbinectedin-gemcitabine combination was synergistic in cell-line-derived pancreatic ductal adenocarcinoma (PDA) xenograft and in patient-derived PDA (AVATAR) mouse models, and to study the mechanisms that could explain the synergism, including changes in pharmacological markers such as γ-H2AX foci formation (as a DSB surrogate marker), capase-3 activation, apoptosis induction and/or inhibition of proliferation. This evidence concerns the gene H2AX and Patent ductus arteriosus.