FOXO and FOXM1 in Cancer: The FOXO-FOXM1 Axis Shapes the Outcome of Cancer Chemotherapy

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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. More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

Source: http://www.ingentaconnect.com/content/ben/cdt/2011/00000012/00000009/art00004

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