title: Anti-EGFR mechanism of action: antitumor effect and underlying cause of adverse events.
abstract: Overexpression of the epidermal growth factor receptor (EGFR) is correlated with poor prognosis in many human cancers. Two main classes of anticancer agents affect the EGFR: those targeting the extracellular ligand-binding domain and those that block the intracellular tyrosine kinase (TK) domain. Cetuximab (Erbitux) is a mouse/human chimeric monoclonal antibody that targets the ligand-binding domain of the EGFR, whereas erlotinib (Tarceva) and gefitinib (Iressa) are small-molecule TK inhibitors. Common toxicities of agents targeting the EGFR differ from those associated with traditional chemotherapy. Given the common pathway through which these agents work, some adverse events are similar. Many patients treated with these agents develop an acne-like rash on the face and upper body, most likely related to keratinocyte alterations and hair follicle proliferation and maturation. Although clinical manifestation of this reaction closely resembles acne vulgaris, the histology is more similar to infectious folliculitis. Other adverse events appear to be related to a drug class or individual agent. For example, interstitial lung disease is a rare but potentially fatal reaction that has been reported with gefitinib. Hypomagnesemia reported in association with cetuximab may be related to EGFR blockade in the kidney. Anaphylactic or anaphylactoid infusion reactions are also seen with cetuximab, as with other monoclonal antibodies.
authors.affiliation: Cancer Genetics, USC/Norris Comprehensive Cancer Center, USC Keck School of Medicine, Los Angeles, California 90033, USA.
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D017486:Acneiform Eruptions / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D066246:ErbB Receptors