ARTICLE | Distillery Therapeutics

Therapeutics: Angiotensin II type 1 receptor (AGTR1)

July 14, 2016 7:00 AM UTC

Patient sample and mouse studies suggest AGTR1 inhibitors could help sensitize obese pancreatic ductal adenocarcinoma (PDAC) patients to chemotherapy. In PDAC patients who underwent surgical tumor resection, adjuvant chemotherapy increased survival in lean but not obese patients, and PDAC tumor samples from obese patients had higher levels of fibrosis than samples from lean patients. In two obese mouse models of PDAC, the AGTR1 inhibitor Cozaar losartan decreased tumor growth and tumor fibrosis compared with no treatment, and Cozaar plus the generic chemotherapy 5-fluorouracil (5-FU) decreased tumor size compared with 5-FU alone. In both models, Cozaar increased tumor blood flow and the fraction of injected 5-FU delivered to tumors. Next steps include testing the effects of AGTR1 inhibition in PDAC models involving radiotherapy or immunotherapy. ...