Browsing by Subject "Antiprogestins"

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    Targeting progesterone signaling prevents metastatic ovarian cancer
    (National Academy of Science, 2020-12-15) Kim, Olga; Park, Eun Young; Kwon, Sun Young; Shin, Sojin; Emerson, Robert E.; Shin, Yong-Hyun; DeMayo, Francesco J.; Lydon, John P.; Coffey, Donna M.; Hawkins, Shannon M.; Quilliam, Lawrence A.; Cheon, Dong-Joo; Fernández, Facundo M.; Nephew, Kenneth P.; Karpf, Adam R.; Widschwendter, Martin; Sood, Anil K.; Bast, Robert C., Jr.; Godwin, Andrew K.; Miller, Kathy D.; Cho, Chi-Heum; Kim, Jaeyeon; Biochemistry and Molecular Biology, School of Medicine
    Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.