The Complexity of Targeting Egfr Signalling in Cancer: from Expression to Turnover.
From: Clinical Experimental Oncology Laboratory, National Cancer Institute, Via Amendola, 209, 70126, Bari, Italy.
Biochimica et biophysica acta
- Publish Date: Aug 2006
- ISSN: 0006-3002
- Volume: 1766
- Issue: 1
- Pages: 120-39
- Medium: Print
- Language: English
- Citation (JAMA): Sebastian Sinto, Settleman Jeffrey, Reshkin Stephan J, et al. The Complexity of Targeting Egfr Signalling in Cancer: from Expression to Turnover.. Biochim. Biophys. Acta Aug 2006;1766:120-39
Abstract
The epidermal growth factor receptor (ErbB1 or EGFR) has been found to be altered in a variety of human cancers. A number of agents targeting these receptors, including specific antibodies directed against the ligand-binding domain of the receptor and small molecules that inhibit kinase activity are either in clinical trials or are already approved for clinical treatment. However, identifying patients that are likely to respond to such treatments has been challenging. As a consequence, it still remains important to identify additional alterations of the tumor cell that contribute to the response to EGFR-targeted agents. While EGFR-mediated signalling pathways have been well established, there is still a rather limited understanding of how intracellular protein-protein interactions, ubiquitination, endocytosis and subsequent degradation of EGFR contribute to the determination of sensitivity to EGFR targeting agents and are emerging areas of investigation. This review primarily focuses on the basic signal transduction pathways mediated through activated membrane bound and/or endosomal EGFR and emphasizes the need to co-target additional proteins that function either upstream or downstream of EGFR to improve cancer therapy.
Mesh Headings (Keywords): Animals, Antineoplastic Agents, Humans, Neoplasms, Receptor, Epidermal Growth Factor, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 16889899
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