Interactions between hypoxia and epidermal growth factor receptor in non-small-cell-lung cancer

Swinson, Daniel E. B. & O'Byrne, Kenneth J. (2006) Interactions between hypoxia and epidermal growth factor receptor in non-small-cell-lung cancer. Clinical Lung Cancer, 7(4), pp. 250-256.

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Tumor hypoxia has been recognized to confer resistance to anticancer therapy since the early 20th century. More recently, its fundamental role in tumorigenesis has been established. Hypoxia-inducible factor (HIF)-1 has been identified as an important transcription factor that mediates the cellular response to hypoxia, promoting both cellular survival and apoptosis under different conditions. Increased tumor cell expression of this transcription factor promotes tumor growth In vivo and is associated with a worse prognosis in patients with non-small-cell lung cancer (NSCLC) undergoing tumor resection. The epidermal growth factor receptor (EGFR) promotes tumor cell proliferation and anglogenesis and inhibits apoptosis. Epidermal growth factor receptor expression increases in a stepwise manner during tumorigenesis and is overexpressed in > 50% of NSCLC tumors. This review discusses the reciprocal relationship between tumor cell hypoxia and EGFR. Recent studies suggest that hypoxia induces expression of EGFR and its ligands. In return, EGFR might enhance the cellular response to hypoxia by increasing expression of HIF-1α, and so act as a survival factor for hypoxic cancer cells. Immunohistochemical studies on a series of resected NSCLC tumors add weight to this contention by demonstrating a close association between expression of EGFR, HIF-1α, and:1 of HIF-1's target proteins, carbonic anhydrase IX. In this article we discuss emerging treatment strategies for NSCLC that target HIF-1, HIF-1 transcriptional targets, and EGFR.

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ID Code: 65774
Item Type: Journal Article
Refereed: Yes
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Keywords: Carbonic anhydrase IX, Hypoxia-inducible factor, Tumor hypoxia, Tumor necrosis, 1 benzyl 3 (5 hydroxymethyl 2 furyl)indazole, 6 [4 (4 ethyl 1 piperazinylmethyl)phenyl] 4 (alpha methylbenzylamino) 7h pyrrolo[2, 3 d]pyrimidine, bevacizumab, carbonate dehydratase IX, carboplatin, DNA topoisomerase inhibitor, docetaxel, epidermal growth factor receptor, epidermal growth factor receptor kinase inhibitor, erlotinib, gefitinib, gemcitabine, hypoxia inducible factor 1alpha, indisulam, ligand, paclitaxel, sorafenib, sulfonamide, transcription factor, vandetanib, vasculotropin inhibitor, antineoplastic activity, apoptosis, bleeding, cancer resistance, cancer surgery, cell proliferation, cell survival, clinical trial, diarrhea, drug eruption, fatigue, gene overexpression, human, hypoxia, immunohistochemistry, in vivo study, lung carcinogenesis, lung non small cell cancer, molecular interaction, nausea, nonhuman, prognosis, protein function, protein targeting, review, tumor cell, tumor growth, tumor vascularization, Anoxia, Carcinoma, Non-Small-Cell Lung, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Lung Neoplasms, Receptor, Epidermal Growth Factor
DOI: 10.3816/CLC.2006.n.002
ISSN: 1525-7304
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2006 Elsevier Inc.
Deposited On: 07 Jan 2014 07:54
Last Modified: 31 Jan 2014 05:32

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