The role of Hedgehog signaling in ovarian cancer

Ovarian epithelial cancer is the most lethal gynecological malignancy.⁶ Because of a lack of effective screening methods for early disease, approximately 75% of ovarian cancers have already spread beyond the ovaries at the time the patient is initially diagnosed.¹⁰ Recent reports suggest that aberrant Hedgehog signaling may contribute to ovarian carcinoma’s proliferative activity.⁶

Current models propose that ligand-dependent Hedgehog signaling may be important in the development of ovarian tumors. Ovarian epithelial cancer cells overexpress the Hedgehog ligand and activate the signaling pathway in neighboring stromal cells.⁵ In turn, stromal fibroblasts may respond by expressing extracellular matrix proteins or secreted factors, such as insulin-like factor, that promote tumor growth or survival.³

In accordance with the ligand-dependent, paracrine-signaling model, mutations in Hedgehog genes have not been detected thus far in ovarian carcinomas. However, strong expression of mammalian Hedgehog ligands, such as Sonic Hedgehog and Desert Hedgehog, has been observed.⁶ Furthermore, increased Hedgehog ligand expression correlates with poor prognosis for ovarian carcinoma patients.⁶ The abnormal activation of Hedgehog signaling in ovarian cancer makes the pathway a potential therapeutic target.