title: Evolving treatment strategies for management of carcinoid tumors.
abstract: Carcinoid tumors of the digestive tract and lungs are neuroendocrine neoplasms with diverse biological features, which vary based on primary tumor location and histological differentiation. Recent years have seen a surge of research on treatments for advanced neuroendocrine tumors. The role of somatostatin analogs has expanded from treatment of the carcinoid syndrome to inhibition of tumor growth. Radiolabeled somatostatin analogs allow for targeted delivery of radiation to somatostatin receptor-expressing tumor cells. A number of biologic agents targeting the VEGF and mTOR pathways have shown promise in randomized clinical trials; however, their role in the treatment of carcinoid tumors remains controversial. This article reviews the evolving treatment strategies for metastatic carcinoid tumors of the aerodigestive tract, with a focus on new systemic targeted agents and liver-directed therapies.
authors.affiliation: Moffitt Cancer Center, 12902 Magnolia Dr., Tampa, FL, 33612, USA, jonathan.strosberg@moffitt.org.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Strosberg
mesh_terms: D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000473:pathology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013004:Somatostatin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
references.citation: AJR Am J Roentgenol. 2003 May;180(5):1379-84
references.pmid: 12704055
references.citation: J Clin Oncol. 2013 Feb 1;31(4):420-5
references.pmid: 23248248
references.citation: Semin Nucl Med. 2006 Apr;36(2):147-56
references.pmid: 16517236
references.citation: Semin Nucl Med. 2002 Apr;32(2):110-22
references.pmid: 11965606
references.citation: N Engl J Med. 1986 Sep 11;315(11):663-6
references.pmid: 2427948
references.citation: Endocrinology. 1992 Apr;130(4):1816-21
references.pmid: 1547711
references.citation: N Engl J Med. 1983 Dec 15;309(24):1495-501
references.pmid: 6139753
references.citation: J Clin Oncol. 2008 Mar 10;26(8):1316-23
references.pmid: 18323556
references.citation: J Clin Oncol. 2009 May 1;27(13):2278-87
references.pmid: 19332717
references.citation: Ann Surg. 2008 Jun;247(6):1029-35
references.pmid: 18520231
references.citation: J Clin Oncol. 2008 Jun 20;26(18):3063-72
references.pmid: 18565894
references.citation: Invest New Drugs. 1997;15(1):77-86
references.pmid: 9195291
references.citation: Ann Oncol. 2013 Jan;24(1):152-60
references.pmid: 22967994
references.citation: J Clin Oncol. 1999 Feb;17(2):600-6
references.pmid: 10080605
references.citation: Cancer. 1998 Dec 1;83(11):2293-301
references.pmid: 9840528
references.citation: J Clin Oncol. 2010 Apr 1;28(10):1652-9
references.pmid: 20194865
references.citation: Clin Cancer Res. 2009 Jan 1;15(1):338-45
references.pmid: 19118063
references.citation: J Clin Oncol. 2008 May 1;26(13):2124-30
references.pmid: 18445841
references.citation: J Clin Oncol. 2011 Jun 10;29(17):2416-23
references.pmid: 21555692
references.citation: Eur J Nucl Med. 2000 Mar;27(3):273-82
references.pmid: 10774879
references.citation: Cancer. 1991 Jul 15;68(2):227-32
references.pmid: 1712661
references.citation: Clin Cancer Res. 2007 May 15;13(10):2986-91
references.pmid: 17505000
references.citation: Biopolymers. 2002;66(6):393-8
references.pmid: 12658726
references.citation: Ann Oncol. 2005 Apr;16(4):525-37
references.pmid: 15728109
references.citation: Hum Pathol. 2003 Jan;34(1):18-27
references.pmid: 12605362
references.citation: Science. 2011 Mar 4;331(6021):1199-203
references.pmid: 21252315
references.citation: Cancer Control. 2006 Jan;13(1):72-8
references.pmid: 16508629
references.citation: JAMA. 1985 May 10;253(18):2741
references.pmid: 2859379
references.citation: Neuroendocrinology. 2013;97(4):318-21
references.pmid: 23296364
references.citation: J Nucl Med. 1994 Oct;35(10):1637-44
references.pmid: 7931662
references.citation: Digestion. 2000;62 Suppl 1:79-83
references.pmid: 10940692
references.citation: N Engl J Med. 2011 Feb 10;364(6):514-23
references.pmid: 21306238
references.citation: Semin Nucl Med. 2002 Apr;32(2):123-32
references.pmid: 11965607
references.citation: Neuroendocrinology. 2013;97(1):74-85
references.pmid: 22237390
references.citation: J Clin Oncol. 2011 Oct 10;29(29):3869-76
references.pmid: 21911723
references.citation: Gastrointest Cancer Res. 2008 May;2(3):113-25
references.pmid: 19259290
references.citation: Cardiovasc Intervent Radiol. 2006 Jul-Aug;29(4):522-9
references.pmid: 16729228
references.citation: World J Surg. 2002 Aug;26(8):985-90
references.pmid: 12016479
references.citation: J Clin Oncol. 2006 Jan 20;24(3):401-6
references.pmid: 16421420
references.citation: Lancet. 1963 Feb 2;1(7275):238-9
references.pmid: 14000847
references.citation: World J Gastroenterol. 2010 Jun 28;16(24):2963-70
references.pmid: 20572298
references.citation: Ann Oncol. 2012 Sep;23(9):2335-2341
references.pmid: 22317769
references.citation: Lung Cancer. 2013 Mar;79(3):289-93
references.pmid: 23286964
references.citation: Radiology. 1993 Nov;189(2):541-7
references.pmid: 7692465
references.citation: J Urol. 1961 Sep;86:321-9
references.pmid: 13763692
references.citation: Am J Clin Oncol. 2008 Jun;31(3):271-9
references.pmid: 18525307
references.citation: AJR Am J Roentgenol. 2003 Oct;181(4):1005-10
references.pmid: 14500219
references.citation: Neuroendocrinology. 2013;97(1):45-56
references.pmid: 22538258
references.citation: Surgery. 1997 Dec;122(6):1147-54; discussion 1154-5
references.pmid: 9426432
references.citation: J Clin Oncol. 2008 Jul 10;26(20):3403-10
references.pmid: 18612155
references.citation: Science. 1973 Jan 5;179(4068):77-9
references.pmid: 4682131
references.citation: Mol Cell Endocrinol. 2008 May 14;286(1-2):69-74
references.pmid: 17977644
references.citation: Semin Oncol. 2002 Apr;29(2):192-5
references.pmid: 11951217
references.citation: N Engl J Med. 1996 Jan 25;334(4):246-54
references.pmid: 8532003
references.citation: Lancet. 2011 Dec 10;378(9808):2005-2012
references.pmid: 22119496
references.citation: J Natl Compr Canc Netw. 2012 Jun 1;10(6):724-64
references.pmid: 22679117
references.citation: Abdom Imaging. 2005 Jul-Aug;30(4):435-41
references.pmid: 15759207
references.citation: Mol Cell Endocrinol. 2008 May 14;286(1-2):40-8
references.pmid: 17913342
references.citation: Endocr Relat Cancer. 2003 Dec;10(4):463-8
references.pmid: 14713259
references.citation: Cancer J. 2003 Jul-Aug;9(4):261-7
references.pmid: 12967136
references.citation: Endocr Relat Cancer. 2012 Sep 14;19(5):657-66
references.pmid: 22807497
references.citation: J Clin Oncol. 2012 Aug 20;30(24):2963-8
references.pmid: 22778320
references.citation: World J Surg. 2001 Jun;25(6):685-8
references.pmid: 11376397
references.citation: Mol Endocrinol. 1999 Jan;13(1):24-37
references.pmid: 9892010
references.citation: Cancer. 1995 Aug 1;76(3):501-9
references.pmid: 8625133
references.citation: Cancer. 2000 Feb 15;88(4):770-6
references.pmid: 10679645
references.citation: J Clin Oncol. 2009 Oct 1;27(28):4656-63
references.pmid: 19704057
references.citation: Gut. 1996 Aug;39(2):279-83
references.pmid: 8977344