An EGFR/HER2-targeted conjugate sensitizes gemcitabine-sensitive and resistant pancreatic cancer through different SMAD4-mediated mechanisms

Chemoresistance is a main limitation for the treatment of pancreatic ductal adenocarcinoma (PDAC). Here, the authors show that an antibody drug conjugate-like compound targeting both EGFR and HER2 overcomes gemcitabine resistance in PDAC preclinical models by mechanisms involving the tumour suppressor SMAD4.