title: Clinical experience with monoclonal antibodies to epidermal growth factor receptor.
abstract: Recent knowledge about the intermediate steps and final consequences of ligand-dependent epidermal growth factor receptor (EGFR) activation has clearly supported the notion that EGFR plays a fundamental role in regulating the proliferation and survival of malignant neoplasms. Among the rationally designed target-based therapeutics that are being assessed, those targeting EGFR appear to be some of the most clinically relevant. The strategy of using monoclonal antibodies (mAbs) to block ligand binding to the extracellular domain of the EGFR has led to the development of therapeutics that robustly arrest malignant cell proliferation and, in some cases, induce profound tumor regression. The chimeric mAb against EGFR, cetuximab, has already been approved by regulatory agencies worldwide to treat patients with advanced colorectal cancer. Other mAbs against EGFR, particularly panitumumab (ABX-EGF), h-R3, and EMD72000, are in advanced stages of clinical development.
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, 7979 Wurzbach Road, 4th Floor, Zeller Building, San Antonio, TX 78229, USA.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Calvo
authors.forename: Eric K
authors.initials: EK
authors.lastname: Rowinsky
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D000077544:Panitumumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab
references.citation: Cancer Res. 1999 Oct 1;59(19):4804-7
references.pmid: 10519388
references.citation: Semin Oncol. 2003 Feb;30(1 Suppl 1):3-11
references.pmid: 12644979
references.citation: Hematol Oncol Clin North Am. 2002 Oct;16(5):1041-63
references.pmid: 12512382
references.citation: Oncogene. 2000 Dec 27;19(56):6550-65
references.pmid: 11426640
references.citation: Cancer Res. 1999 Mar 15;59(6):1236-43
references.pmid: 10096554
references.citation: Cancer Res. 2002 Jun 15;62(12):3335-9
references.pmid: 12067969
references.citation: J Clin Oncol. 2004 Aug 1;22(15):3003-15
references.pmid: 15210739
references.citation: Crit Rev Oncol Hematol. 2001 Apr;38(1):17-23
references.pmid: 11255078
references.citation: Clin Cancer Res. 2003 Apr;9(4):1274-83
references.pmid: 12684395
references.citation: Proc Natl Acad Sci U S A. 1986 Jun;83(11):3825-9
references.pmid: 2424012
references.citation: Cancer Res. 1993 Oct 1;53(19):4637-42
references.pmid: 8402640
references.citation: Br J Cancer. 2004 Aug 2;91(3):418-24
references.pmid: 15238978
references.citation: Cancer Chemother Pharmacol. 2001 Jun;47(6):519-24
references.pmid: 11459205
references.citation: Clin Cancer Res. 2001 Dec;7(12):4230-8
references.pmid: 11751524
references.citation: Blood. 1997 Nov 1;90(9):3322-31
references.pmid: 9345014
references.citation: Semin Oncol. 2002 Feb;29(1 Suppl 4):47-50
references.pmid: 11894013
references.citation: J Clin Oncol. 2004 May 1;22(9):1646-54
references.pmid: 15117987
references.citation: Semin Oncol. 2002 Oct;29(5 Suppl 14):3-9
references.pmid: 12422308
references.citation: J Clin Oncol. 2002 May 15;20(10):2495-9
references.pmid: 12011127
references.citation: Annu Rev Med. 2004;55:433-57
references.pmid: 14746530
references.citation: J Clin Oncol. 2003 Jul 15;21(14):2787-99
references.pmid: 12860957
references.citation: Cancer Immunol Immunother. 1998 May;46(3):167-73
references.pmid: 9625540
references.citation: Clin Cancer Res. 2002 Nov;8(11):3496-502
references.pmid: 12429640
references.citation: Nat Med. 2000 Apr;6(4):443-6
references.pmid: 10742152
references.citation: Clin Cancer Res. 1995 Nov;1(11):1311-8
references.pmid: 9815926
references.citation: J Biol Chem. 1994 Nov 4;269(44):27595-602
references.pmid: 7961676
references.citation: Semin Oncol. 2003 Jun;30(3 Suppl 7):3-14
references.pmid: 12840796
references.citation: Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):984-90
references.pmid: 14967460
references.citation: Cancer Res. 2004 Aug 1;64(15):5355-62
references.pmid: 15289342
references.citation: N Engl J Med. 2004 Jul 22;351(4):337-45
references.pmid: 15269313
references.citation: Oncologist. 2002;7 Suppl 4:2-8
references.pmid: 12202782
references.citation: Nucl Med Biol. 1999 Apr;26(3):275-9
references.pmid: 10363798
references.citation: J Clin Oncol. 2004 Jan 1;22(1):175-84
references.pmid: 14701780
references.citation: J Clin Oncol. 2002 Sep 15;20(18 Suppl):1S-13S
references.pmid: 12235219
references.citation: Oncology (Williston Park). 2003 Nov;17(11 Suppl 12):11-6
references.pmid: 14682118
references.citation: J Natl Cancer Inst. 1993 Aug 18;85(16):1327-33
references.pmid: 8340945
references.citation: Cancer Res. 2001 Dec 15;61(24):8887-95
references.pmid: 11751413
references.citation: Cancer Treat Rev. 2004 May;30(3):255-68
references.pmid: 15059649
references.citation: Eur J Cancer. 2001 Sep;37 Suppl 4:S16-22
references.pmid: 11597400
references.citation: J Clin Oncol. 2004 Apr 1;22(7):1177-9
references.pmid: 14993229
references.citation: J Clin Oncol. 2004 Apr 1;22(7):1201-8
references.pmid: 14993230
references.citation: Oncologist. 2004;9(1):58-67
references.pmid: 14755015