Targeting progesterone signaling prevents metastatic ovarian cancer

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.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Kim O, Park EY, Kwon SY, et al. Targeting progesterone signaling prevents metastatic ovarian cancer. Proc Natl Acad Sci U S A. 2020;117(50):31993-32004. doi:10.1073/pnas.2013595117
ISSN
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Proceedings of the National Academy of Sciences (PNAS)
Rights
Publisher Policy
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Final published version
This item is under embargo {{howLong}}