Targeting progesterone signaling prevents metastatic ovarian cancer
Olga Kim, Eun Young Park, Sun Young Kwon, So‐Jin Shin, Robert E. Emerson, Yong-Hyun Shin, Francesco J. DeMayo, John P. Lydon, Donna 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
Abstract
Significance Why women carrying a pathogenic germline BRCA1 mutation are predisposed to ovarian and breast cancer remains elusive. This study points to ovarian progesterone as a culprit. Generally, BRCA1 -mutation carriers exhibit high yet individually varying levels of progesterone during the menstrual cycle. Although not all BRCA1 -mutation carriers develop these cancers, all of them are advised to undergo prophylactic surgeries at a young age (under 40 y to 45 y) to prevent ovarian and breast cancer. Insights from robust in vivo findings in this study offer a novel concept: Targeting progesterone signaling with antiprogestins could be an effective nonsurgical prophylactic option for ovarian and breast cancer prevention for these high-risk women.