Targeting progesterone signaling prevents metastatic ovarian cancer

Olga Kim, Eun Young Park, Sun Young Kwon, Sojin Shin, Robert E. Emerson, Yong Hyun Shin, Francesco J. DeMayo, John P. Lydon, Donna M. Coffey, Shannon M. Hawkins, Lawrence A. Quilliam, Dong Joo Cheon, Facundo M. Fernández, Kenneth P. Nephew, Adam R. Karpf, Martin Widschwendter, Anil K. Sood, Robert C. Bast, Andrew K. Godwin, Kathy D. MillerChi Heum Cho, Jaeyeon Kim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31993-32004
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number50
DOIs
StatePublished - Dec 15 2020

Keywords

  • Antiprogestins
  • BRCA
  • Hormone
  • Ovarian cancer
  • Progesterone

ASJC Scopus subject areas

  • General

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