title: Tumor biology and cancer therapy - an evolving relationship.
abstract: The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pathways underlie cancer, and not just altered genes. Thus, an effective therapeutic agent will sometimes have to target downstream parts of a signaling pathway or physiological effects rather than individual genes. In addition, over the past few years increasing evidence has suggested that solid tumors represent a very heterogeneous group of cells with different susceptibility to cancer therapy. Thus, since therapeutic concepts and pathophysiological understanding are continuously evolving a combination of current concepts in tumor therapy and tumor biology is needed. This review aims to present current problems of cancer therapy by highlighting exemplary results from recent clinical trials with colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying reasons.
authors.affiliation: Department of Internal Medicine I, University of Ulm, Albert Einstein Allee 23, 89081 Ulm, Germany. goetz.wichert@uniklinik-ulm.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seufferlein
authors.forename: Johann
authors.initials: J
authors.lastname: Ahn
authors.forename: Denis
authors.initials: D
authors.lastname: Krndija
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lother
authors.forename: Guido
authors.initials: G
authors.lastname: Adler
authors.forename: Götz
authors.initials: G
authors.lastname: von Wichert
references.citation: Nat Med. 2001 Sep;7(9):1028-34
references.pmid: 11533706
references.citation: J Exp Med. 1971 Feb 1;133(2):275-88
references.pmid: 4332371
references.citation: J Histochem Cytochem. 2008 Nov;56(11):977-93
references.pmid: 18645205
references.citation: Cancer Res. 2001 Sep 15;61(18):6624-8
references.pmid: 11559524
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14228-33
references.pmid: 15381773
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530
references.citation: Am J Respir Cell Mol Biol. 2004 May;30(5):671-7
references.pmid: 14672915
references.citation: Oligonucleotides. 2007 Summer;17(2):201-12
references.pmid: 17638524
references.citation: Ann Oncol. 2007 Apr;18(4):782-8
references.pmid: 17218488
references.citation: Science. 2001 Nov 9;294(5545):1299-304
references.pmid: 11701921
references.citation: Cell. 2008 May 16;133(4):704-15
references.pmid: 18485877
references.citation: Nature. 1993 Apr 29;362(6423):841-4
references.pmid: 7683111
references.citation: Cancer Cell. 2009 Mar 3;15(3):232-9
references.pmid: 19249681
references.citation: J Mol Histol. 2004 Mar;35(3):233-45
references.pmid: 15339043
references.citation: Nat Med. 2006 Oct;12(10):1167-74
references.pmid: 16998484
references.citation: J Clin Oncol. 2008 Dec 10;26(35):5705-12
references.pmid: 19001320
references.citation: J Exp Clin Cancer Res. 2008 Nov 04;27:62
references.pmid: 18983683
references.citation: Blood. 2007 Dec 15;110(13):4427-35
references.pmid: 17804695
references.citation: Cancer Res. 2008 Mar 15;68(6):1953-61
references.pmid: 18339877
references.citation: Cancer Cell. 2003 Jun;3(6):565-76
references.pmid: 12842085
references.citation: Nat Clin Pract Oncol. 2009 Jan;6(1):10-1
references.pmid: 18957948
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14920-5
references.pmid: 14657333
references.citation: N Engl J Med. 2008 Oct 23;359(17):1757-65
references.pmid: 18946061
references.citation: N Engl J Med. 2004 Jun 3;350(23):2335-42
references.pmid: 15175435
references.citation: J Clin Oncol. 2005 Apr 10;23(11):2445-59
references.pmid: 15753456
references.citation: Nat Med. 2009 Jan;15(1):59-67
references.pmid: 19098908
references.citation: Nat Prod Rep. 1995 Jun;12(3):271-6
references.pmid: 7792073
references.citation: J Clin Oncol. 2008 Apr 20;26(12):2006-12
references.pmid: 18421053
references.citation: Cancer Biol Ther. 2006 Oct;5(10):1304-12
references.pmid: 16929176
references.citation: Cancer Invest. 2008 Feb;26(1):81-95
references.pmid: 18181050
references.citation: Nat Rev Cancer. 2003 Jun;3(6):459-65
references.pmid: 12778136
references.citation: Cancer Res. 2007 May 15;67(10):4827-33
references.pmid: 17510412
references.citation: Lancet. 2006 Oct 14;368(9544):1329-38
references.pmid: 17046465
references.citation: J Clin Oncol. 2003 Jul 15;21(14):2787-99
references.pmid: 12860957
references.citation: Cancer Metastasis Rev. 2006 Dec;25(4):521-9
references.pmid: 17186383
references.citation: Cancer Res. 2006 Aug 1;66(15):7445-52
references.pmid: 16885340
references.citation: J Clin Oncol. 2008 Apr 1;26(10):1626-34
references.pmid: 18316791
references.citation: J Clin Oncol. 2007 May 20;25(15):1960-6
references.pmid: 17452677
references.citation: Science. 2008 Sep 26;321(5897):1807-12
references.pmid: 18772396
references.citation: J Gastroenterol. 2008;43(12):905-11
references.pmid: 19107333
references.citation: Nat Rev Clin Oncol. 2009 Apr;6(4):190-1
references.pmid: 19333222
references.citation: J Clin Oncol. 2009 Feb 10;27(5):672-80
references.pmid: 19114685
references.citation: Int J Cancer. 2008 May 15;122(10):2255-9
references.pmid: 18224685
references.citation: Nat Rev Cancer. 2008 Aug;8(8):592-603
references.pmid: 18650835
references.citation: N Engl J Med. 2007 Dec 27;357(26):2666-76
references.pmid: 18160686
references.citation: Science. 2001 Nov 9;294(5545):1343-6
references.pmid: 11598267
references.citation: Nat Med. 2002 Sep;8(9):979-86
references.pmid: 12185362
references.citation: Gastroenterology. 2005 Oct;129(4):1237-50
references.pmid: 16230077
references.citation: Gastrointest Cancer Res. 2008 Jul;2(4 Suppl):S16-9
references.pmid: 19343141
references.citation: Eur J Cancer. 2006 Jun;42(9):1293-7
references.pmid: 16644203
references.citation: Cancer Cell. 2009 Mar 3;15(3):220-31
references.pmid: 19249680
references.citation: Clin Colorectal Cancer. 2004 Oct;4 Suppl 2:S62-8
references.pmid: 15479481
references.citation: Science. 2002 Feb 22;295(5559):1526-8
references.pmid: 11859195
references.citation: N Engl J Med. 2005 Feb 3;352(5):476-87
references.pmid: 15689586
references.citation: J Exp Med. 1996 Apr 1;183(4):1797-806
references.pmid: 8666936
references.citation: Neuro Oncol. 2008 Dec;10(6):940-5
references.pmid: 18708344
references.citation: J Clin Oncol. 2007 Oct 10;25(29):4557-61
references.pmid: 17876013
references.citation: Cancer Res. 2002 Mar 15;62(6):1730-6
references.pmid: 11912147
references.citation: Cell Stem Cell. 2007 Oct 11;1(4):353-5
references.pmid: 18371369
references.citation: Nat Rev Cancer. 2008 Mar;8(3):167-79
references.pmid: 18256617
references.citation: Biol Blood Marrow Transplant. 2008 Nov;14(11):1253-61
references.pmid: 18940680
references.citation: J Clin Oncol. 2007 Aug 1;25(22):3230-7
references.pmid: 17664471
references.citation: Br J Cancer. 2007 Apr 23;96(8):1166-9
references.pmid: 17375050
references.citation: Cell Stem Cell. 2007 Sep 13;1(3):313-23
references.pmid: 18371365
references.citation: N Engl J Med. 2009 Apr 2;360(14):1408-17
references.pmid: 19339720
references.citation: Nature. 2006 Dec 21;444(7122):1083-7
references.pmid: 17183323
references.citation: Ann Surg Oncol. 2008 Feb;15(2):649-54
references.pmid: 17987340
references.citation: Ann Oncol. 2000 Jul;11(7):785-92
references.pmid: 10997804
references.citation: J Clin Pharmacol. 2005 Aug;45(8):872-7
references.pmid: 16027397
references.citation: N Engl J Med. 1971 Nov 18;285(21):1182-6
references.pmid: 4938153
references.citation: Cell. 2006 Jan 13;124(1):175-89
references.pmid: 16413490
references.citation: J Clin Oncol. 2005 Jun 1;23(16):3706-12
references.pmid: 15867200
references.citation: Clin Colorectal Cancer. 2005 May;5(1):24-6
references.pmid: 15929803
references.citation: J Clin Oncol. 2006 Sep 10;24(26):4293-300
references.pmid: 16908937
references.citation: Cancer Res. 2008 Jun 1;68(11):4022-5
references.pmid: 18519657
references.citation: Lancet Oncol. 2008 May;9(5):402-3
references.pmid: 18452847
references.citation: Br J Cancer. 2008 Jan 15;98(1):71-6
references.pmid: 18059397
references.citation: J Clin Oncol. 2008 Mar 20;26(9):1443-51
references.pmid: 18349394
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12443-8
references.pmid: 16107537
references.citation: Cell Cycle. 2008 Jan 15;7(2):188-93
references.pmid: 18256530
references.citation: Nature. 2002 Aug 29;418(6901):934
references.pmid: 12198537
references.citation: Leukemia. 2002 Apr;16(4):650-7
references.pmid: 11960346
references.citation: Stem Cells. 2005 Aug;23(7):879-94
references.pmid: 15888687
references.citation: N Engl J Med. 2008 Oct 23;359(17):1834-6
references.pmid: 18946069
references.citation: J Clin Oncol. 2005 Nov 1;23(31):8033-40
references.pmid: 16258101
references.citation: J Clin Oncol. 2006 Jan 1;24(1):16-24
references.pmid: 16330672
references.citation: J Clin Oncol. 1997 Jun;15(6):2403-13
references.pmid: 9196156
references.citation: Curr Opin Cell Biol. 2007 Apr;19(2):223-9
references.pmid: 17303407
references.citation: Mol Cancer. 2006 Dec 02;5:67
references.pmid: 17140455
references.citation: J Clin Oncol. 2008 Jan 20;26(3):374-9
references.pmid: 18202412
references.citation: J Clin Invest. 2008 Jun;118(6):2111-20
references.pmid: 18497886
references.citation: Nat Rev Cancer. 2009 Apr;9(4):265-73
references.pmid: 19262571
references.citation: Br J Cancer. 2007 Oct 22;97(8):1139-45
references.pmid: 17940504
references.citation: Cancer Res. 1989 Sep 1;49(17):4682-9
references.pmid: 2547513
references.citation: Stem Cells. 2007 Jul;25(7):1645-53
references.pmid: 17412894
references.citation: Cancer Res. 2007 Feb 1;67(3):1030-7
references.pmid: 17283135
references.citation: J Cell Biochem. 2008 Jan 1;103(1):245-55
references.pmid: 17549698
references.citation: PLoS One. 2008 Jun 18;3(6):e2428
references.pmid: 18560594
references.citation: Science. 2008 Sep 26;321(5897):1801-6
references.pmid: 18772397
references.citation: Clin Colorectal Cancer. 2008 May;7(3):162
references.pmid: 18621632
references.citation: N Engl J Med. 2009 Feb 5;360(6):563-72
references.pmid: 19196673
references.citation: J Clin Oncol. 2005 Jun 20;23(18):4162-71
references.pmid: 15867205
references.citation: Cell. 2006 Nov 17;127(4):679-95
references.pmid: 17110329
references.citation: Cell Stem Cell. 2007 Oct 11;1(4):389-402
references.pmid: 18371377
references.citation: World J Gastroenterol. 2008 Apr 21;14(15):2308-13
references.pmid: 18416455
references.citation: J Dig Dis. 2008 Feb;9(1):1-7
references.pmid: 18251787
references.citation: J Clin Oncol. 2008 Apr 10;26(11):1907-8; author reply 1908-9
references.pmid: 18398161
references.citation: Science. 2007 Nov 16;318(5853):1108-13
references.pmid: 17932254
references.citation: Clin Colorectal Cancer. 2005 May;5(1):21-3
references.pmid: 15929802
references.citation: J Clin Oncol. 2009 May 1;27(13):2231-7
references.pmid: 19307500