Targeting progesterone signaling prevents metastatic ovarian cancer.
Olga KimEun Young ParkSun Young KwonSojin ShinRobert E EmersonYong-Hyun ShinFrancesco J DeMayoJohn P LydonDonna M CoffeyShannon M HawkinsLawrence A QuilliamDong-Joo CheonFacundo M FernándezKenneth P NephewAdam R KarpfMartin WidschwendterAnil K SoodRobert C BastAndrew K GodwinKathy D MillerChi-Heum ChoJaeyeon KimPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
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.
Keyphrases
- high grade
- estrogen receptor
- mouse model
- papillary thyroid
- squamous cell carcinoma
- small cell lung cancer
- randomized controlled trial
- endothelial cells
- genome wide
- squamous cell
- copy number
- low grade
- cancer therapy
- type diabetes
- drug delivery
- high throughput
- dna methylation
- polycystic ovary syndrome
- pregnant women
- adipose tissue
- skeletal muscle
- childhood cancer
- smoking cessation
- cervical cancer screening