Journal
EXPERT REVIEW OF ANTICANCER THERAPY
Volume 12, Issue 1, Pages 51-62Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1586/ERA.11.194
Keywords
beta-catenin; canonical Wnt signaling; carcinogenesis; endometrial cancer; novel therapeutic targets; Wnt antagonists
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Funding
- institutional NIH
- Ruth L Kirschstein NRSA [2 T32 CA-060396-11]
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While the role of Wnt signaling is well established in colorectal carcinogenesis, its function in gynecologic cancers has not been elucidated. Here, we describe the current state of knowledge of canonical Wnt signaling in endometrial cancer (EC), and its implications for future therapeutic targets. Deregulation of the Wnt/beta-catenin signaling pathway in EC occurs by inactivating beta-catenin mutations in approximately 10-45% of ECs, and via downregulation of Wnt antagonists by epigenetic silencing. The Wnt pathway is intimately involved with estrogen and progesterone, and emerging data implicate it in other important signaling pathways, such as mTOR and Hedgehog. While no therapeutic agents targeting the Wnt signaling pathway are currently in clinical trials, the preclinical data presented suggest a role for Wnt signaling in uterine carcinogenesis, with further research warranted to elucidate the mechanism of action and to proceed towards targeted cancer drug development.
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