Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer.
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Publication year
2008Source
Lancet Oncology, 9, 3, (2008), pp. 288-96ISSN
Publication type
Article / Letter to editor
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Organization
Radiation Oncology
Journal title
Lancet Oncology
Volume
vol. 9
Issue
iss. 3
Page start
p. 288
Page end
p. 96
Subject
ONCOL 3: Translational research; UMCN 1.3: Tumor microenvironmentAbstract
Activation of the phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (AKT) pathway is associated with three major radioresistance mechanisms: intrinsic radioresistance; tumour-cell proliferation; and hypoxia. Monitoring and manipulation of this signal-transduction pathway can have important implications for the management of head and neck cancer, because activation of the PI3-K/AKT pathway is a frequent event in these tumours. PI3-K/AKT signalling regulates cellular processes, including proliferation, invasion, apoptosis, and the upregulation of hypoxia-related proteins. Activation of this pathway can be caused by stimulation of receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR). In clinical trials, a strong and independent association has been noted between expression of activated AKT and treatment outcome. Therefore, the search for molecular predictors of sensitivity to EGFR-directed treatment should be extended to markers of PI3-K/AKT activation. Another strategy might be the direct targeting and inhibition of this pathway. Such inhibition will enhance the efficacy of radiotherapy, by antagonising radiation-induced cellular defense mechanisms, especially in tumours that have activated the PI3-K/AKT cascade. Thus, the activation status of this pathway might be a key element for the prediction of treatment response and for therapeutic targeting in head and neck cancer.
This item appears in the following Collection(s)
- Academic publications [238430]
- Electronic publications [122512]
- Faculty of Medical Sciences [90359]
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