Targeting Wnt Signaling in Endometrial Cancer.

This review presents new findings on Wnt signaling in endometrial carcinoma and implications
for possible future treatments. The Wnt proteins are essential mediators in cell signaling
during vertebrate embryo development. Recent biochemical and genetic studies have provided
significant insight into Wnt signaling, in particular in cell cycle regulation, inflammation, and cancer.
The role of Wnt signaling is well established in gastrointestinal and breast cancers, but its function in
gynecologic cancers, especially in endometrial cancers, has not been well elucidated. Development of
a subset of endometrial carcinomas has been attributed to activation of the APC/�-catenin signaling
pathway (due to �-catenin mutations) and downregulation of Wnt antagonists by epigenetic silencing.
The Wnt pathway also appears to be linked to estrogen and progesterone, and new findings
implicate it in mTOR and Hedgehog signaling. Therapeutic interference of Wnt signaling remains a
significant challenge. Herein, we discuss the Wnt-activating mechanisms in endometrial cancer and
review the current advances and challenges in drug discovery.