Progesterone and FOXO1 signaling: Harnessing cellular senescence for the treatment of ovarian cancer

open access

"....The inference is that progestins, compounds widely used for a variety of clinical indications, could also be valuable in the management of ovarian cancer, the most lethal of all gynecological malignancies.....

"The present study not only identifies the PR-FOXO1 axis as a potential therapeutic target in ovarian cancer, but also helps to explain why expression of PR is a prognostic marker for ovarian cancer associated with longer progression-free survival. Similarly, this study provides a mechanistic explanation for why pregnancy, which is associated with high circulating progesterone levels, and the use of progestin-containing oral contraceptives may suppress the growth of premalignant cells in the ovarian cortex, thus protecting against ovarian cancer.⁴ There are, however, major obstacles that limit the clinical use of progestins in ovarian cancer. Foremost, ovarian cancer is a heterogeneous disease that consists of etiologically distinct tumors that share an anatomical site. Consequently, progestin sensitivity is likely restricted to certain histological types, such endometrioid and serous cancers.⁴ Further, PR as well as FOXO1 are frequently lost in ovarian cancer; the robustness of the senescence response in vivo has not yet been studied, and the contribution of putative non-genomic progestin receptors in modulating cellular responses to hormonal therapies remains poorly understood and controversial.^5........