Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma

著者: Yanxia Zhao, Jinghong Cao, Alexander Melamed, Michael J. Worley, Allison Gockley, Dennis Jones, Hadi T. Nia, Yanling Zhang, Triantafyllos Stylianopoulos, Ashwin S. Kumar, Fotios Mpekris, Meenal Datta, Yao Sun, Limeng Wu, Xing Gao, Oladapo Yeku, Marcela G. del Carmen, David R. Spriggs, Rakesh K. Jain, Lei Xu - Proceedings of the National Academy of Sciences, PNAS 2019 被引用: 259

Significance Despite initial responsiveness to chemotherapy, the overwhelming majority of advanced ovarian cancer patients relapse with resistant disease. Thus, developing more effective strategies for ovarian cancer treatment is a high clinical priority. Here, we report that targeting angiotensin signaling with losartan, an angiotensin receptor blocker, can reduce extracellular matrix in ovarian tumors and the associated physical barriers that normally hinder drug delivery and efficacy. These changes in the tumor microenvironment lead to improved response to chemotherapy, and, importantly, decrease ascites—a major burden for ovarian cancer patients. These preclinical findings are in concert with our retrospective analysis showing improved survival in patients receiving angiotensin system inhibitors concurrently with standard treatment for ovarian cancer and should be tested in a clinical trial.