RESUMEN
The epidermal growth factor receptor (EGFR) family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). These receptors consist of an extracellular domain, a single hydrophobic transmembrane segment, and an intracellular portion with a juxtamembrane segment, a protein kinase domain, and a carboxyterminal tail. The ErbB proteins function as homo and heterodimers. Growth factor binding to EGFR induces a large conformational change in the extracellular domain. Two ligand-EGFR complexes unite to form a back-to-back dimer in which the ligands are on opposite sides of the aggregate. Following ligand binding, EGFR intracellular kinase domains form an asymmetric dimer. The carboxyterminal lobe of the activator kinase of the dimer interacts with the amino-terminal lobe of the receiver kinase thereby leading to its allosteric stimulation. Several malignancies are associated with the mutation or increased expression of members of the ErbB family including lung, breast, stomach, colorectal, head and neck, and pancreatic carcinomas. Gefitinib, erlotinib, and afatinib are orally effective protein-kinase targeted quinazoline derivatives that are used in the treatment of ERBB1-mutant lung cancer and lapatinib is an orally effective quinazoline derivative used in the treatment of ErbB2-overexpressing breast cancer. Moreover, monoclonal antibodies that target the extracellular domain of ErbB2 are used for the treatment of ErbB2-positive breast cancer and monoclonal antibodies that target ErbB1 and are used for the treatment of colorectal cancer. Cancers treated with these targeted drugs eventually become resistant to them, and a current goal of research is to develop drugs that are effective against drug-resistant tumors.