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The FOXO3-FOXM1 Axis: a key cancer drug target and a modulator of cancer drug resistance

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Title: The FOXO3-FOXM1 Axis: a key cancer drug target and a modulator of cancer drug resistance
Authors: Yao, S
Fan, YN
Lam, EW
Item Type: Journal Article
Abstract: The FOXO3 and FOXM1 forkhead box transcription factors, functioning downstream of the essential PI3K-Akt, Ras-ERK and JNK/p38MAPK signalling cascades, are crucial for cell proliferation, differentiation, cell survival, senescence, DNA damage repair and cell cycle control. The development of resistance to both conventional and newly emerged molecularly targeted therapies is a major challenge confronting current cancer treatment in the clinic. Intriguingly, the mechanisms of resistance to ‘classical’ cytotoxic chemotherapeutics and to molecularly targeted therapies are invariably linked to deregulated signalling through the FOXO3 and FOXM1 transcription factors. This is owing to the involvement of FOXO3 and FOXM1 in the regulation of genes linked to crucial drug action-related cellular processes, including stem cell renewal, DNA repair, cell survival, drug efflux, and deregulated mitosis. A better understanding of the mechanisms regulating the FOXO3-FOXM1 axis, as well as their downstream transcriptional targets and functions, may render these proteins reliable and early diagnostic/prognostic factors as well as crucial therapeutic targets for cancer treatment and importantly, for overcoming chemotherapeutic drug resistance.
Issue Date: 1-Jun-2018
Date of Acceptance: 23-Nov-2017
URI: http://hdl.handle.net/10044/1/54182
DOI: https://dx.doi.org/10.1016/j.semcancer.2017.11.018
ISSN: 1044-579X
Publisher: Elsevier
Start Page: 77
End Page: 89
Journal / Book Title: Seminars in Cancer Biology
Volume: 50
Copyright Statement: © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Imperial College Trust
Breast Cancer Campaign
Cancer Research UK
Breast Cancer Now
Breast Cancer Now
Medical Research Council (MRC)
Funder's Grant Number: BBS/B/03785
Keywords: 1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Online Publication Date: 2017-11-24
Appears in Collections:Department of Surgery and Cancer