However, the preclinical data on the improvement of tumor perfusion by ETBR are unclear: the EBTR agonist IRL-1620 improves tumor perfusion in some animal models of [136,137] and causes severe vasoconstriction in other [138,139], whereas bosentan, a dual ETR antagonist, significantly improved tumor perfusion in pancreatic cancer [77]. This evidence concerns the gene EDNRB and familial pancreatic carcinoma.