Dedes, K. J., Wetterskog, D., Ashworth, A., Kaye, S. B., Reis, J. S. (2011) Emerging therapeutic targets in endometrial cancer. NATURE REVIEWS CLINICAL ONCOLOGY, 8 (5). pp. 261-271. ISSN 1759-4774

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Abstract

Endometrial cancer comprises a heterogeneous group of tumors, with distinct risk factors, clinical presentation, histopathological features and molecular characteristics. Currently, treatment of metastatic or recurrent disease is based on conventional chemotherapy combination regimens. Advances in the understanding of the molecular pathology of the two types of endometrial carcinoma-type I (endometrioid) and type II (non-endometrioid)-have underpinned the first steps in the development and testing of targeted therapies. Of the potential therapeutic targets identified to date, clinical trials have only assessed the efficacy of inhibition of the EGFR, VEGFR and PI3K/PTEN/AKT/mTOR signaling pathways; responses to these targeted therapies were modest. Despite the striking molecular differences between type I and type II endometrial cancers, most clinical trials have not taken this diversity into account. The identification of activating mutations of kinases (for example PIK3CA and FGFR2) and loss of function of genes related to DNA repair (for example PTEN) may lead to more biology-driven clinical trials exploiting the concepts of oncogene addiction and synthetic lethality.

Item Type:	Review Article
Authors (ICR Faculty only):	Reis-Filho, Jorge and Kaye, Stan and Ashworth, Alan
All Authors:	Dedes, K. J., Wetterskog, D., Ashworth, A., Kaye, S. B., Reis, J. S.
Additional Information:	ISI Document Delivery No.: 758GG Times Cited: 0 Cited Reference Count: 139 Dedes, Konstantin J. Wetterskog, Daniel Ashworth, Alan Kaye, Stan B. Reis-Filho, Jorge S. Swiss National Science Foundation (SNF) [128, 487]; Breakthrough Breast Cancer ; National Health Service The authors of this Review are funded in part by Breakthrough Breast Cancer. K. J. Dedes is funded in part by a Fellowship of the Swiss National Science Foundation (SNF Grant 128,487). The authors acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Center. Nature publishing group New york
Uncontrolled Keywords:	i phosphatidylinositide 3-kinases serous papillary carcinoma factor receptor expression surgically staged patients gynecologic-oncology-group different histologic types metastatic breast-cancer mixed mullerian tumors e-cadherin expression clear-cell carcinoma
Research teams:	Closed research groups > Molecular Pathology ICR divisions > Breast Cancer Research > Gene Function ICR divisions > Molecular Pathology > Gene Function ICR divisions > Cancer Therapeutics > Medicine (Kaye Drug Development Unit) ICR divisions > Clinical Studies > Medicine (Kaye Drug Development Unit)
Depositing User:	Barry Jenkins
Date Deposited:	25 May 2011 15:00
Last Modified:	24 Feb 2014 16:23
URI:	http://publications.icr.ac.uk/id/eprint/10708

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