title: Cancer stem cells: a stride towards cancer cure?
abstract: Despite major refinements in cancer therapy drugs, our progress at increasing the cure rates of most cancers has been hampered by high relapse rates. A possible biological explanation of the high frequency of relapse and resistance to currently available drugs has been provided by the cancer stem cell (CSC) proposition. Basically, the CSC theory hypothesizes the presence of a hierarchically organized, relatively rare population of cells that is responsible for tumor initiation, self-renewal and maintenance, mutation accumulation and therapy resistance. Since first postulated by John Dick, multiple reports have provided support for this hypothesis by isolating (more or less) rare cell populations, where the ability to initiate tumors in vivo has been demonstrated. Most progress and stronger data supporting this theory are found predominantly in myelogenous leukemias, whose study has benefited from over half-a-century progress in our understanding of the normal hierarchical organization of hematopoiesis. This review, however, also analyzes the advancement in the quantitative and functional analysis of solid tumor stem cells and in the analysis of the tumor microenvironment as specialized, nurturing niches for CSCs. Overall, this review intends to briefly summarize most of the evidences that support the CSC theory and the apparent contradictions, if not skepticism from the scientific community, about its validity for all forms of cancer, or alternatively on just a few cancers initiated by a limited number of somatic or germinal mutations.
authors.affiliation: Division of Experimental Hematology & Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Amitava
authors.initials: A
authors.lastname: Sengupta
authors.forename: Jose A
authors.initials: JA
authors.lastname: Cancelas
mesh_terms: D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic; D004777:Environment; D006801:Humans; D016130:Immunophenotyping; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor
references.citation: Nature. 2006 Dec 7;444(7120):756-60
references.pmid: 17051156
references.citation: Nat Med. 2006 Oct;12(10):1167-74
references.pmid: 16998484
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63
references.pmid: 17548814
references.citation: Cell. 2005 Jun 17;121(6):823-35
references.pmid: 15960971
references.citation: Blood. 2009 Dec 24;114(27):5415-25
references.pmid: 19797526
references.citation: Nature. 2010 Apr 8;464(7290):852-7
references.pmid: 20305640
references.citation: Nat Med. 2006 Apr;12(4):446-51
references.pmid: 16565722
references.citation: Blood. 2002 Sep 1;100(5):1532-42
references.pmid: 12176867
references.citation: Science. 2010 Mar 26;327(5973):1650-3
references.pmid: 20339075
references.citation: Blood. 2010 May 6;115(18):3704-7
references.pmid: 20207983
references.citation: Blood. 2010 Jul 8;116(1):81-4
references.pmid: 20407032
references.citation: Cell Stem Cell. 2007 Oct 11;1(4):389-402
references.pmid: 18371377
references.citation: Cancer Cell. 2008 Feb;13(2):153-66
references.pmid: 18242515
references.citation: Blood. 2008 Aug 1;112(3):568-75
references.pmid: 18523148
references.citation: Nature. 2008 Dec 4;456(7222):593-8
references.pmid: 19052619
references.citation: Cell. 2007 Jun 15;129(6):1097-110
references.pmid: 17574023
references.citation: Nat Med. 2005 Jun;11(6):630-7
references.pmid: 15908956
references.citation: Nature. 2006 Jan 12;439(7073):212-5
references.pmid: 16227971
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14720-5
references.pmid: 11121071
references.citation: Nat Med. 2006 Oct;12(10):1175-80
references.pmid: 16998483
references.citation: Science. 2003 Oct 17;302(5644):445-9
references.pmid: 14564009
references.citation: Nature. 2006 Dec 7;444(7120):761-5
references.pmid: 17151667
references.citation: Blood. 2004 Sep 15;104(6):1648-55
references.pmid: 15178579
references.citation: Nat Med. 2005 Aug;11(8):886-91
references.pmid: 16025125
references.citation: Nat Med. 1997 Dec;3(12):1337-45
references.pmid: 9396603
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Cancer Cell. 2008 Jan;13(1):69-80
references.pmid: 18167341
references.citation: Nat Med. 1997 Jul;3(7):730-7
references.pmid: 9212098
references.citation: Science. 2007 Jul 20;317(5836):337
references.pmid: 17641192
references.citation: Nat Immunol. 2004 Jul;5(7):738-43
references.pmid: 15170211
references.citation: Cancer Cell. 2007 Jan;11(1):69-82
references.pmid: 17222791
references.citation: Leukemia. 2007 May;21(5):949-55
references.pmid: 17361218
references.citation: Science. 2009 Jun 26;324(5935):1670-3
references.pmid: 19556499
references.citation: Nature. 2004 Nov 18;432(7015):396-401
references.pmid: 15549107
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8
references.pmid: 17210912
references.citation: Cell Stem Cell. 2007 Nov;1(5):555-67
references.pmid: 18371393
references.citation: Nature. 2003 May 15;423(6937):255-60
references.pmid: 12714970
references.citation: Blood. 2008 Dec 15;112(13):4793-807
references.pmid: 19064739
references.citation: J Exp Med. 1996 Apr 1;183(4):1797-806
references.pmid: 8666936
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5103-8
references.pmid: 17372229
references.citation: Cancer Cell. 2008 Feb;13(2):105-16
references.pmid: 18242511
references.citation: Nature. 2009 Dec 3;462(7273):595-601
references.pmid: 19898493
references.citation: N Engl J Med. 2004 Aug 12;351(7):657-67
references.pmid: 15306667
references.citation: Nature. 2008 Jan 17;451(7176):345-9
references.pmid: 18202660
references.citation: Cell Stem Cell. 2009 Jul 2;5(1):31-42
references.pmid: 19570512
references.citation: Nature. 2005 Dec 8;438(7069):820-7
references.pmid: 16341007
references.citation: Cancer Cell. 2008 Jun;13(6):483-95
references.pmid: 18538732
references.citation: Cancer Res. 2005 Dec 1;65(23):10946-51
references.pmid: 16322242
references.citation: Cancer Cell. 2007 Nov;12(5):467-78
references.pmid: 17996650
references.citation: Nature. 2009 Apr 9;458(7239):776-9
references.pmid: 19169242
references.citation: Cell Death Differ. 2008 Mar;15(3):504-14
references.pmid: 18049477
references.citation: Science. 2008 Dec 19;322(5909):1861-5
references.pmid: 19095944
references.citation: Cell Stem Cell. 2009 Feb 6;4(2):129-40
references.pmid: 19200802
references.citation: Nat Rev Cancer. 2008 Oct;8(10):755-68
references.pmid: 18784658
references.citation: Cancer Res. 2006 Aug 15;66(16):7843-8
references.pmid: 16912155
references.citation: Cell Stem Cell. 2007 Sep 13;1(3):313-23
references.pmid: 18371365
references.citation: Blood. 2004 Jun 1;103(11):4010-22
references.pmid: 14982876
references.citation: Leukemia. 2007 Dec;21(12):2559-61
references.pmid: 17611557
references.citation: Nature. 2007 Jan 4;445(7123):106-10
references.pmid: 17122772
references.citation: Cell Stem Cell. 2010 Mar 5;6(3):265-78
references.pmid: 20207229
references.citation: Blood. 2002 Jan 1;99(1):310-8
references.pmid: 11756186
references.citation: Cell Stem Cell. 2008 Dec 4;3(6):658-69
references.pmid: 19041782
references.citation: Nat Rev Drug Discov. 2009 Oct;8(10):806-23
references.pmid: 19794444
references.citation: Cancer Cell. 2002 Oct;2(4):289-300
references.pmid: 12398893
references.citation: Cancer Res. 2007 Feb 1;67(3):1030-7
references.pmid: 17283135
references.citation: Biochem Biophys Res Commun. 2007 Nov 23;363(3):578-83
references.pmid: 17897629