title: Targeting the epidermal growth factor receptor (EGFR)--a new therapeutic option in oncology?
abstract: The epidermal growth factor receptor (EGFR) is commonly overexpressed in a variety of solid tumours, and clinical trials indicate that this antigen has important roles in cancer aetiology and progression. EGFR thus provides a rational target for cancer therapies and a number of strategies influencing this receptor, and its downstream signal cascades, including monoclonal antibodies, tyrosine-kinase inhibitors, antisense oligonucleotides inhibiting EGFR synthesis and antibody-based immunoconjugates, have been evaluated. In particular, monoclonal antibodies targeting the receptor's extracellular domain and small molecules blocking tyrosine-kinase activation intracellularly have already shown some activity in clinical phase I-III trials. These two major classes of anti-EGFR therapeutics will be the main topic of this review. In the case of tyrosine-kinase inhibitors, amplification, high polysomy of the EGFR gene, high protein expression and mutations of the receptor were found to be significantly associated with better response to such treatment. However, many questions remain unanswered and future issues in the development of EGFR inhibitors will include the identification of biological predictors of response, combination with other therapies and also their use in earlier stages of cancer.
authors.affiliation: Division of Oncology, University Hospital Basel, Switzerland. mamotc@uhbs.ch
authors.forename: Christoph
authors.initials: C
authors.lastname: Mamot
authors.forename: Christoph
authors.initials: C
authors.lastname: Rochlitz
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors