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FOXO and FOXM1 in cancer : the FOXO-FOXM1 axis shapes the outcome of cancer chemotherapy
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Wilson, Miranda S. C., Brosens, Jan J., Schwenen, Helma D. C. and Lam, Eric W.-F. (2011) FOXO and FOXM1 in cancer : the FOXO-FOXM1 axis shapes the outcome of cancer chemotherapy. Current Drug Targets, Vol.12 (No.9). pp. 1256-1266. doi:10.2174/138945011796150244 ISSN 1389-4501.
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Official URL: http://www.bentham.org/cdt
Abstract
FOXO transcription factors, functioning downstream of the PI3K-PTEN-AKT (PKB) signalling cascade, are essential for cell proliferation, differentiation, DNA damage repair and apoptosis. Recent research indicates that the related transcription factor FOXM1 is a direct target of repression by FOXO proteins. Inactivation of FOXO or overexpression of FOXM1 is associated with tumorigenesis and cancer progression. In addition, the cytostatic and cytotoxic effects of a diverse spectrum of anti-cancer drugs, such as paclitaxel, doxorubicin, lapatinib, gefitinib, imatinib and cisplatin, are mediated through the activation of FOXO3a and/or the inhibition of its target FOXM1. Paradoxically, FOXO proteins also contribute to drug resistance by driving the expression of genes important for drug efflux as well as DNA repair and cell survival pathways in drug resistant cancers. Given its pivotal roles in drug sensitivity as well as resistance, targeting the FOXO-FOXM1 axis could be a viable strategy for treatment of cancer and for overcoming drug resistance. Studying the expression profiles of the components of the FOXO-FOXM1 axis and their cofactors in cancer patients might also help to predict and monitor their clinical response to chemotherapy. A better understanding of the mechanism by which FOXO and FOXM1 are regulated, as well as their roles in drug sensitivity and resistance, may render these proteins crucial prognostic markers and therapeutic targets for breast cancer and other malignancies.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > R Medicine (General) | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Current Drug Targets | ||||
| Publisher: | Bentham Science Publishers Ltd. | ||||
| ISSN: | 1389-4501 | ||||
| Official Date: | August 2011 | ||||
| Dates: |
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| Volume: | Vol.12 | ||||
| Number: | No.9 | ||||
| Number of Pages: | 11 | ||||
| Page Range: | pp. 1256-1266 | ||||
| DOI: | 10.2174/138945011796150244 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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