Targeting progesterone signaling prevents metastatic ovarian cancer
Targeting progesterone signaling prevents metastatic ovarian cancer
复制标题
DOI：
10.1073/pnas.2013595117
复制
发表时间：
2020-12-15
影响因子：
11.1
通讯作者：
Kim, Jaeyeon
中科院分区：
文献类型：
--
作者：
Kim, Olga;Park, Eun Young;Kim, Jaeyeon
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 (similar to 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.
