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Radiother Oncol. 2013 Sep;108(3):370-7. doi: 10.1016/j.radonc.2013.06.010. Epub 2013 Jul 3.

Nuclear EGFR as a molecular target in cancer.

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1
Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Wisconsin Institute for Medical Research, Madison, USA.

Abstract

The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell's nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future.

KEYWORDS:

BCRP; COX-2; Cancer; DNA protein kinase; DNA-PK; EGFR; HNSCC; INM; LMP1; MUC1; NLS; NPC; NSLC; Nuclear EGFR; ONM; PCNA; PNPase; RHA; RNA helicase A; Resistance; TAT interacting protein; TIF2; TIP3; TKI; TNBC; breast cancer resistant protein; cyclooxygenase-2; epidermal growth factor receptor; head and neck squamous cell carcinoma; iNOS; inner nuclear membrane; latent membrane protein 1; mucin-1; nitric oxide synthase; non-small cell lung cancer; nuclear localization sequence; nuclear localization signal; nuclear pore complex; outer nuclear membrane; polynucleotide phosphorylase; proliferating cell nuclear antigen; transcriptional intermediary factor 2; triple negative breast cancer; tyrosine kinase inhibitor

PMID:
23830194
PMCID:
PMC3818450
DOI:
10.1016/j.radonc.2013.06.010
[Indexed for MEDLINE]
Free PMC Article
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