ErbB receptors in the biology and pathology of the aerodigestive tract.
The most common sites of malignancies in the aerodigestive tract include the lung, head and neck and the esophagus. Esophageal adenocarcinomas (EA), esophageal squamous cell carcinomas (ESCC), and squamous cell carcinomas of the head and neck (SCCHN) are the primary focus of this review. Traditional treatment for aerodigestive tract cancers includes primary chemoradiotherapy (CRT) or surgical resection followed by radiation (or CRT). Recent developments in treatment have focused increasingly on molecular targeting strategies including cetuximab (a monoclonal antibody against epidermal growth factor receptor (EGFR)). Cetuximab was FDA approved in 2006 for treatment of SCCHN, underscoring the importance of understanding the biology of these malignancies. EGFR is a member of the ErbB family of growth factor receptor tyrosine kinases. The major pathways activated by ErbB receptors include Ras/Raf/MAPK; PI3K/AKT; PLCgamma and STATs, all of which lead to the transcription of target genes that may contribute to aerodigestive tumor progression. This review explores the expression of ErbB receptors in EA, ESCC and SCCHN and the signaling pathways of EGFR in SCCHN.
Morgan
Sarah
S
Department of Otolaryngology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite 500, Pittsburgh, PA 15213, USA.
Grandis
Jennifer R
JR
D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D018739:Oncogene Proteins v-erbB / Q000145:classification / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D018739:Oncogene Proteins v-erbB; D050791:STAT Transcription Factors; D066246:ErbB Receptors; D019061:src-Family Kinases
Anticancer Res. 2004 Mar-Apr;24(2B):811-9
15161032
Cancer Metastasis Rev. 2005 Jan;24(1):47-69
15785872
Exp Mol Pathol. 2008 Apr;84(2):79-89
18279851
Ann Intern Med. 1999 Jun 1;130(11):883-90
10375336
Clin Cancer Res. 2006 Jul 1;12(13):4103-11
16818711
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8602-6
2236070
Nature. 1995 Jul 27;376(6538):337-41
7630400
Pharmacol Ther. 2004 Apr;102(1):37-46
15056497
Oncol Rep. 2008 Aug;20(2):373-8
18636200
Nature. 1995 Nov 23;378(6555):390-4
7477376
Int J Cancer. 2007 Feb 15;120(4):781-7
17096332
Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):391-5
17980508
J Cancer Res Clin Oncol. 2005 Feb;131(2):111-9
15672286
Science. 2001 Dec 7;294(5549):2179-81
11679632
Cancer Res. 1993 Aug 1;53(15):3579-84
8339264
J Clin Oncol. 2006 Jun 10;24(17):2666-72
16763281
Pathol Res Pract. 2005;201(6):417-25
16136747
Br J Cancer. 2005 Apr 11;92(7):1253-60
15785739
Head Neck. 1999 May;21(3):204-10
10208662
Cancer Res. 2001 Sep 1;61(17):6500-10
11522647
Nat Rev Cancer. 2005 May;5(5):341-54
15864276
Oncol Rep. 2007 Apr;17(4):887-93
17342332
J Clin Oncol. 2007 Jun 1;25(16):2164-70
17538160
J Biol Chem. 2003 Aug 22;278(34):31574-83
12771142
Int J Oncol. 2005 May;26(5):1177-85
15809707
Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4283-7
16857803
Nat Med. 1996 Feb;2(2):237-40
8574972
Cancer Res. 1991 Apr 15;51(8):2164-72
2009534
Curr Opin Cell Biol. 2003 Apr;15(2):143-8
12648669
Oral Oncol. 2002 Oct;38(7):627-40
12167415
Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4227-32
10760290
Ai Zheng. 2005 Feb;24(2):241-5
15694044
Cancer Lett. 1995 Aug 16;95(1-2):79-83
7656248
N Engl J Med. 2007 May 10;356(19):1944-56
17494927
Oncogene. 2000 May 15;19(21):2474-88
10851046
Exp Cell Res. 2003 Mar 10;284(1):99-110
12648469
Cancer Treat Res. 2003;114:15-60
12619537
Clin Cancer Res. 1999 Jul;5(7):1862-7
10430093
Onkologie. 2004 Feb;27(1):17-21
15007244
Semin Radiat Oncol. 2007 Jan;17(1):2-9
17185192
J Natl Cancer Inst. 1998 Jan 21;90(2):150-5
9450576
Anticancer Res. 2001 May-Jun;21(3B):1953-63
11497283
Cancer Invest. 2001;19(5):554-68
11458821
Br J Cancer. 2005 Jul 11;93(1):107-15
15986037
Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1323-7
14630269
Cancer Causes Control. 2001 Oct;12(8):721-32
11562112
Int J Radiat Oncol Biol Phys. 1989 Sep;17(3):467-76
2674075
Oncogene. 2005 Sep 1;24(38):5897-904
16007209
Cancer. 1994 Oct 1;74(7):1933-8
8082099
Oral Oncol. 2001 Oct;37(7):599-604
11564582
J Pathol. 2001 Oct;195(3):343-8
11673832
Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):903-13
14967450
Cancer Res. 2003 Oct 15;63(20):6763-71
14583472
Curr Drug Targets. 2005 May;6(3):243-57
15857286
Int J Cancer. 2006 Mar 1;118(5):1173-80
16161046
Curr Oncol Rep. 2001 Jan;3(1):66-71
11123872
Head Neck. 2007 Jul;29(7):655-64
17315173
Dis Esophagus. 2006;19(4):224-31
16866851
Clin Cancer Res. 2003 Oct 15;9(13):5028-35
14581378
Nature. 1995 Nov 23;378(6555):394-8
7477377
Cell Oncol. 2007;29(4):327-34
17641416
J Clin Pathol. 2006 Jun;59(6):631-4
16731604
Am J Gastroenterol. 1999 Jul;94(7):1933-40
10406262
Curr Oncol Rep. 2003 Mar;5(2):140-6
12583831
Nature. 1994 Feb 3;367(6462):474-6
8107807
Front Biosci. 2008 Jan 01;13:1857-65
17981673
Cancer Causes Control. 2000 Mar;11(3):231-8
10782657
Cancer J. 2001 Mar-Apr;7(2):108-11
11324763
Cancer Res. 2007 Aug 15;67(16):7907-16
17699797
Int J Cancer. 2008 Mar 15;122(6):1303-10
18000824
Mutat Res. 2000 Apr;462(2-3):335-42
10767643
Eur J Surg Oncol. 1997 Feb;23(1):30-5
9066744
Cell. 1992 Aug 7;70(3):401-10
1643658
Sci STKE. 2006 Jul 18;2006(344):re6
16849649
Proc Natl Acad Sci U S A. 2006 May 2;103(18):6901-6
16641105
ORL J Otorhinolaryngol Relat Spec. 2004;66(1):21-6
15103197
Clin Cancer Res. 2007 Oct 1;13(19):5869-75
17908981
Expert Opin Biol Ther. 2007 Feb;7(2):257-68
17250463
J Surg Oncol. 2005 Dec 1;92(3):169-90
16299787
Expert Opin Biol Ther. 2006 Mar;6(3):231-41
16503733
J Cell Biochem. 2007 Oct 1;102(2):311-9
17661350
Clin Cancer Res. 1998 Jan;4(1):13-20
9516947
Oncology. 2007;73(1-2):104-11
18337622
Clin Exp Metastasis. 2003;20(4):285-90
12856715
Curr Treat Options Oncol. 2007 Jun;8(3):239-51
17962911
Am J Pathol. 1999 Apr;154(4):965-73
10233832
Mod Pathol. 2007 Jan;20(1):120-9
17143264
Oncogene. 2007 Apr 5;26(16):2353-64
17043653
Nature. 1997 Oct 16;389(6652):725-30
9338783
Oral Oncol. 2002 Jan;38(1):73-80
11755824
Head Neck. 2003 Jan;25(1):67-73
12478546
J Surg Oncol. 2008 Jan 1;97(1):44-50
18000820
Int J Oncol. 1998 Aug;13(2):375-8
9664135
Structure. 2008 Mar;16(3):460-7
18334220
Cancer. 1989 Jun 1;63(11):2169-73
2720567
Eur J Surg Oncol. 2007 Feb;33(1):44-8
17142003
Dis Esophagus. 2007;20(1):9-11
17227303
Am J Physiol Gastrointest Liver Physiol. 2004 Dec;287(6):G1227-37
15284024
Oncogene. 2003 Sep 18;22(40):6183-93
13679857
Semin Oncol. 2004 Dec;31(6):734-43
15599851
Cancer Epidemiol Biomarkers Prev. 1997 May;6(5):369-77
9149898
Acta Med Okayama. 2006 Feb;60(1):25-34
16508686
Am J Pathol. 2004 Oct;165(4):1315-29
15466396
Anticancer Res. 1998 Nov-Dec;18(6B):4793-800
9891559
Mol Cell Biol. 1998 Feb;18(2):790-8
9447975
Cancer Res. 2003 Sep 1;63(17):5629-35
14500405
Science. 2007 May 18;316(5827):1039-43
17463250
Clin Cancer Res. 1999 Dec;5(12):4164-74
10632356
Gastroenterology. 2001 Dec;121(6):1286-93
11729107
J Natl Cancer Inst. 1998 Jun 3;90(11):824-32
9625170
Ann Surg Oncol. 2007 Feb;14(2):977-91
17122988
Int J Cancer. 2008 Sep 15;123(6):1422-8
18546259
Exp Cell Res. 2003 Mar 10;284(1):66-77
12648466
Mol Cell Proteomics. 2005 Apr;4(4):356-76
15657067
Gut. 2005 Mar;54 Suppl 1:i1-5
15711002
Mol Pharmacol. 2008 Jun;73(6):1632-42
18326051
J Clin Oncol. 2006 Apr 1;24(10):1612-9
16575012
JAMA. 2007 Jul 4;298(1):70-82
17609492
Clin Cancer Res. 2006 Sep 15;12(18):5268-72
17000658
Head Neck. 2008 May;30(5):667-74
18383530
Int J Cancer. 2000 Dec 1;88(5):759-65
11072245
Cancer. 1996 Sep 15;78(6):1284-92
8826952
Mol Cancer Ther. 2007 Apr;6(4):1414-24
17431120
Cancer. 2007 Feb 15;109(4):658-67
17211865
World J Surg. 1999 Oct;23(10):1010-8
10512940
J Pathol. 2004 Nov;204(3):317-25
15476268
Oncology (Williston Park). 2006 Apr;20(5 Suppl 2):15-25
16736979
Cancer Res. 2004 Dec 15;64(24):9139-43
15604284
Clin Cancer Res. 2006 Sep 1;12(17):5064-73
16951222
J Biol Chem. 2000 Oct 6;275(40):30934-42
10908564
Nat Clin Pract Oncol. 2005 Jun;2(6):315-24
16264989
N Engl J Med. 2006 Feb 9;354(6):567-78
16467544
Diagn Mol Pathol. 2006 Sep;15(3):125-30
16932066
J Clin Invest. 1998 Oct 1;102(7):1385-92
9769331
Expert Opin Ther Targets. 2006 Oct;10(5):639-47
16981821
Am J Gastroenterol. 1997 Feb;92(2):212-5
9040193
Med Oral. 2003 Nov-Dec;8(5):374-81
14595263