The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies.
BACKGROUND
Understanding and identifying molecular biology and genetics of endometrial cancer are central to the development of novel therapies. This article reviews the molecular basis for genesis of endometrial cancer with regard to pathogenesis, classification, and implications for targeted therapies.


METHODS
Genes and cellular pathways that may have an important role in endometrial cancers, both endometrioid and nonendometrioid cancers, are identified. Recently studied drugs and potential future drugs that target some of these genes and pathways are reviewed.


RESULTS
The most frequent genetic alteration of endometrioid endometrial cancer is PTEN. PI3CA and K-ras mutations are less common but are often associated with PTEN. Alterations in MLH1 and MSH6 are documented with microsatellite instability. Beta-catenin has a minor but significant association. Conversely, p53 mutation is more often associated with nonendometrioid cancer; others being inactivation of p16 and/or overexpression of HER-2/neu. Absence of E-cadherin is more often than not present in nonendometrioid cancers and is associated with poor prognosis. Novel agents that target the AKT-PI3K-mTOR pathway and those that inhibit epidermal growth factor receptor (EGFR), vascular endothelial growth factors (VEGF), fibroblast growth factor receptor 2 (FGFR2), and folate receptors are currently being investigated.


CONCLUSIONS
Novel targeted agents, either alone or in combination with cytotoxic agents, may result in superior treatment for patients.
Bansal
Nisha
N
Gynecologic Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Yendluri
Vimala
V
Wenham
Robert M
RM
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D016889:Endometrial Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans
D000970:Antineoplastic Agents