Our combined data support a general clinical evaluation of GPER1 and its ligands as chemoenhancing modifiers in the pharmacological targeting of PDAC.12 In this context, it is worth pointing out that PDAC is genetically a highly complex disease44 and the potential therapeutic advantages and disadvantages with selective GPER1 agonists and antagonists are complex and not fully understood.45 One major limitation of pancreatic cancer therapy is inadequate drug penetration due to high levels of desmoplasia. This evidence concerns the gene GPER1 and familial pancreatic carcinoma.