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Nuclear EGFR as a molecular target in cancer.
- Source :
-
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2013 Sep; Vol. 108 (3), pp. 370-7. Date of Electronic Publication: 2013 Jul 03. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Celecoxib
Cell Line, Tumor
Drug Resistance, Neoplasm
ErbB Receptors physiology
Humans
Proliferating Cell Nuclear Antigen physiology
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Pyrazoles pharmacology
Radiation Tolerance
Sulfonamides pharmacology
ErbB Receptors antagonists & inhibitors
Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0887
- Volume :
- 108
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 23830194
- Full Text :
- https://doi.org/10.1016/j.radonc.2013.06.010