The complexity of targeting EGFR signalling in cancer: from expression to turnover.

摘要: The epidermal growth factor receptor (ErbB1 or EGFR) has been found to be altered in a variety of human cancers. A number agents targeting these receptors, including specific antibodies directed against the ligand-binding domain and small molecules that inhibit kinase activity are either clinical trials already approved for treatment. However, identifying patients likely respond such treatments challenging. As consequence, it still remains important identify additional alterations tumor cell contribute response EGFR-targeted agents. While EGFR-mediated signalling pathways have well established, there is rather limited understanding how intracellular protein-protein interactions, ubiquitination, endocytosis subsequent degradation EGFR determination sensitivity emerging areas investigation. This review primarily focuses on basic signal transduction mediated through activated membrane bound and/or endosomal emphasizes need co-target proteins function upstream downstream improve cancer therapy.