title: Pharmacology of epidermal growth factor inhibitors.
abstract: Research into the molecular bases of malignant diseases has yielded the development of many novel agents with potential antitumor activity. Evidence for a causative role for the epidermal growth factor receptor (EGFR), which is now regarded as an excellent target for cancer chemotherapy in human cancer, leads to the development of EGFR inhibitors. Two classes of anti-EGFR agents are currently in clinical use: monoclonal antibodies directed at the extracellular domain of the receptor, and the low-molecular-weight receptor tyrosine kinase inhibitors acting intracellularly by competing with adenosine triphosphate for binding to the tyrosine kinase portion of the EGFR. The effect on the receptor interferes with key biological functions including cell cycle arrest, potentiation of apoptosis, inhibition of angiogenesis and cell invasion and metastasis. Cetuximab, a monoclonal antibody, and the receptor tyrosine kinase inhibitors gefitinib and erlotinib are currently approved for the treatment of patients with cancer. New agents with clinical activity are entering the clinic, and new combinatorial approaches are being explored with the aim of improving the potency and pharmacokinetics of EGFR inhibition, to increase the synergistic activity in combination with chemotherapy and overcome resistance to the EGFR inhibitors.
authors.affiliation: Clinical and Experimental Pharmacology, Centro di Riferimento Oncologico, Aviano, Pordenone, Italy. gtoffoli@cro.it
authors.forename: G
authors.initials: G
authors.lastname: Toffoli
authors.forename: E
authors.initials: E
authors.lastname: De Mattia
authors.forename: E
authors.initials: E
authors.lastname: Cecchin
authors.forename: P
authors.initials: P
authors.lastname: Biason
authors.forename: S
authors.initials: S
authors.lastname: Masier
authors.forename: G
authors.initials: G
authors.lastname: Corona
mesh_terms: D000634:Aminoquinolines; D000814:Aniline Compounds; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D000077341:Lapatinib; D000077339:Leflunomide; D009025:Morpholines / Q000494:pharmacology; D009930:Organic Chemicals / Q000494:pharmacology; D000077544:Panitumumab; D010880:Piperidines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: C107875:6-(methylamino)pyrido(3,4-d)pyrimidine; D000634:Aminoquinolines; D000814:Aniline Compounds; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007555:Isoxazoles; D009025:Morpholines; D009930:Organic Chemicals; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011687:Purines; D011743:Pyrimidines; D011758:Pyrroles; D011799:Quinazolines; D011804:Quinolines; C501637:TheraCIM; C518939:monoclonal antibody 806; D000077341:Lapatinib; D000077544:Panitumumab; C410026:PKI 166; C420268:Canertinib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C489254:AEE 788; D000077339:Leflunomide; C487932:neratinib; C520777:matuzumab; D000068818:Cetuximab; D000077156:Gefitinib; C413879:EKB 569; C452423:vandetanib