Home>>The anti-EGFR antibody cetuximab sensitizes human head and neck squamous cell carcinoma cells to radiation in part through inhibiting radiation-induced upregulation of HIF-1α

Search

About

Authors:
Address: Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA; The Graduate School of Biomedical Sciences, The University of Texas, Health Science Center at Houston, Houston, TX 77030, USA.
Journal:

Publication:

abstract

In this study, we investigated The mechanisms underlying cetuximab-mediated radiosensitization of HNSCC. Irradiation of HNSCC cells upregulated hypoxia-inducible factor-1 alpha (HIF-1α) via a mechanism involving de novo synthesis of HIF-1α protein. Radiation-induced upregulation of HIF-1α was completely abolished by concurrent treatment of HNSCC cells with cetuximab. Experimental elevation of constitutively expressed HIF-1α abolished cetuximab-mediated radiosensitization in HNSCC cells, whereas downregulation of HIF-1α by siRNA or a small molecule inhibitor enhanced responses of cetuximab-resistant HNSCC cells to cetuximab plus radiation. Our data suggest that cetuximab sensitizes cancer cells to ionizing radiation in part through inhibition of radiation-induced upregulation of HIF-1α.

Related Articles
Responses of cancer cells with wild-type or tyrosine kinase domain-mutated epidermal growth factor receptor (EGFR) to EGFR-targeted therapy are linked to downregulation of hypoxia-inducible factor-1alpha.
Mol Cancer. 2007
Responses of cancer cells with wild-type or tyrosine kinase domain-mutated epidermal growth factor receptor (EGFR) to EGFR-targeted therapy are linked to downregulation of hypoxia-inducible factor-1alpha.
Lu Y, Liang K, Li X, Fan Z. Mol Cancer. 2007 Oct 11; 6:63. Epub 2007 Oct 11.
Requirement of hypoxia-inducible factor-1alpha down-regulation in mediating the antitumor activity of the anti-epidermal growth factor receptor monoclonal antibody cetuximab.
Mol Cancer Ther. 2008
Requirement of hypoxia-inducible factor-1alpha down-regulation in mediating the antitumor activity of the anti-epidermal growth factor receptor monoclonal antibody cetuximab.
Li X, Lu Y, Liang K, Pan T, Mendelsohn J, Fan Z. Mol Cancer Ther. 2008 May; 7(5):1207-17.
1, 9-Pyrazoloanthrones downregulate HIF-1α and sensitize cancer cells to cetuximab-mediated anti-EGFR therapy.
PLoS One. 2010
1, 9-Pyrazoloanthrones downregulate HIF-1α and sensitize cancer cells to cetuximab-mediated anti-EGFR therapy.
Lu Y, Li X, Lu H, Fan Z. PLoS One. 2010 Dec 29; 5(12):e15823. Epub 2010 Dec 29.
Review Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody.
Drugs Today (Barc). 2005
Review Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody.
Harding J, Burtness B. Drugs Today (Barc). 2005 Feb; 41(2):107-27.
Review The role of cetuximab in the treatment of squamous cell cancer of the head and neck.
Expert Opin Biol Ther. 2005
Review The role of cetuximab in the treatment of squamous cell cancer of the head and neck.
Burtness B. Expert Opin Biol Ther. 2005 Aug; 5(8):1085-93.