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Publication : Targeting progesterone signaling prevents metastatic ovarian cancer.

First Author  Kim O Year  2020
Journal  Proc Natl Acad Sci U S A Volume  117
Issue  50 Pages  31993-32004
PubMed ID  33262282 Mgi Jnum  J:341505
Mgi Id  MGI:6490578 Doi  10.1073/pnas.2013595117
Citation  Kim O, et al. (2020) Targeting progesterone signaling prevents metastatic ovarian cancer. Proc Natl Acad Sci U S A 117(50):31993-32004
abstractText  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 ( approximately 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.
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