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. Miller; Chi Heum Cho; Jaeyeon Kim

doi:10.1073/pnas.2013595117

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 journal › Article › peer-review

31 Scopus citations

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 language	English (US)
Pages (from-to)	31993-32004
Number of pages	12
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	117
Issue number	50
DOIs	https://doi.org/10.1073/pnas.2013595117
State	Published - Dec 15 2020

Keywords

Antiprogestins
BRCA
Hormone
Ovarian cancer
Progesterone

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.2013595117

Cite this

Kim, O., Park, E. Y., Kwon, S. Y., Shin, S., Emerson, R. E., Shin, Y. H., DeMayo, F. J., Lydon, J. P., Coffey, D. M., Hawkins, S. M., Quilliam, L. A., Cheon, D. J., Fernández, F. M., Nephew, K. P., Karpf, A. R., Widschwendter, M., Sood, A. K., Bast, R. C., Godwin, A. K., ... Kim, J. (2020). Targeting progesterone signaling prevents metastatic ovarian cancer. Proceedings of the National Academy of Sciences of the United States of America, 117(50), 31993-32004. https://doi.org/10.1073/pnas.2013595117

Kim, O, Park, EY, Kwon, SY, Shin, S, Emerson, RE, Shin, YH, DeMayo, FJ, Lydon, JP, Coffey, DM, Hawkins, SM, Quilliam, LA, Cheon, DJ, Fernández, FM, Nephew, KP, Karpf, AR, Widschwendter, M, Sood, AK, Bast, RC, Godwin, AK, Miller, KD, Cho, CH & Kim, J 2020, 'Targeting progesterone signaling prevents metastatic ovarian cancer', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 50, pp. 31993-32004. https://doi.org/10.1073/pnas.2013595117

@article{291239a8e91d4fa39e923af1e8e352ec,

title = "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.",

keywords = "Antiprogestins, BRCA, Hormone, Ovarian cancer, Progesterone",

author = "Olga Kim and Park, {Eun Young} and Kwon, {Sun Young} and Sojin Shin and Emerson, {Robert E.} and Shin, {Yong Hyun} and DeMayo, {Francesco J.} and Lydon, {John P.} and Coffey, {Donna M.} and Hawkins, {Shannon M.} and Quilliam, {Lawrence A.} and Cheon, {Dong Joo} and Fern{\'a}ndez, {Facundo M.} and Nephew, {Kenneth P.} and Karpf, {Adam R.} and Martin Widschwendter and Sood, {Anil K.} and Bast, {Robert C.} and Godwin, {Andrew K.} and Miller, {Kathy D.} and Cho, {Chi Heum} and Jaeyeon Kim",

year = "2020",

month = dec,

day = "15",

doi = "10.1073/pnas.2013595117",

language = "English (US)",

volume = "117",

pages = "31993--32004",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "50",

}

TY - JOUR

T1 - Targeting progesterone signaling prevents metastatic ovarian cancer

AU - Kim, Olga

AU - Park, Eun Young

AU - Kwon, Sun Young

AU - Shin, Sojin

AU - Emerson, Robert E.

AU - Shin, Yong Hyun

AU - DeMayo, Francesco J.

AU - Lydon, John P.

AU - Coffey, Donna M.

AU - Hawkins, Shannon M.

AU - Quilliam, Lawrence A.

AU - Cheon, Dong Joo

AU - Fernández, Facundo M.

AU - Nephew, Kenneth P.

AU - Karpf, Adam R.

AU - Widschwendter, Martin

AU - Sood, Anil K.

AU - Bast, Robert C.

AU - Godwin, Andrew K.

AU - Miller, Kathy D.

AU - Cho, Chi Heum

AU - Kim, Jaeyeon

PY - 2020/12/15

Y1 - 2020/12/15

N2 - 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.

AB - 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.

KW - Antiprogestins

KW - BRCA

KW - Hormone

KW - Ovarian cancer

KW - Progesterone

UR - http://www.scopus.com/inward/record.url?scp=85098469877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85098469877&partnerID=8YFLogxK

U2 - 10.1073/pnas.2013595117

DO - 10.1073/pnas.2013595117

M3 - Article

C2 - 33262282

AN - SCOPUS:85098469877

SN - 0027-8424

VL - 117

SP - 31993

EP - 32004

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 50

ER -

Targeting progesterone signaling prevents metastatic ovarian cancer

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this