Cancer stem cells: a stride towards cancer cure?
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.
Sengupta
Amitava
A
Division of Experimental Hematology & Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Cancelas
Jose A
JA
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*
D014408:Biomarkers, Tumor
Nature. 2006 Dec 7;444(7120):756-60
17051156
Nat Med. 2006 Oct;12(10):1167-74
16998484
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10158-63
17548814
Cell. 2005 Jun 17;121(6):823-35
15960971
Blood. 2009 Dec 24;114(27):5415-25
19797526
Nature. 2010 Apr 8;464(7290):852-7
20305640
Nat Med. 2006 Apr;12(4):446-51
16565722
Blood. 2002 Sep 1;100(5):1532-42
12176867
Science. 2010 Mar 26;327(5973):1650-3
20339075
Blood. 2010 May 6;115(18):3704-7
20207983
Blood. 2010 Jul 8;116(1):81-4
20407032
Cell Stem Cell. 2007 Oct 11;1(4):389-402
18371377
Cancer Cell. 2008 Feb;13(2):153-66
18242515
Blood. 2008 Aug 1;112(3):568-75
18523148
Nature. 2008 Dec 4;456(7222):593-8
19052619
Cell. 2007 Jun 15;129(6):1097-110
17574023
Nat Med. 2005 Jun;11(6):630-7
15908956
Nature. 2006 Jan 12;439(7073):212-5
16227971
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14720-5
11121071
Nat Med. 2006 Oct;12(10):1175-80
16998483
Science. 2003 Oct 17;302(5644):445-9
14564009
Nature. 2006 Dec 7;444(7120):761-5
17151667
Blood. 2004 Sep 15;104(6):1648-55
15178579
Nat Med. 2005 Aug;11(8):886-91
16025125
Nat Med. 1997 Dec;3(12):1337-45
9396603
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
12629218
Cancer Cell. 2008 Jan;13(1):69-80
18167341
Nat Med. 1997 Jul;3(7):730-7
9212098
Science. 2007 Jul 20;317(5836):337
17641192
Nat Immunol. 2004 Jul;5(7):738-43
15170211
Cancer Cell. 2007 Jan;11(1):69-82
17222791
Leukemia. 2007 May;21(5):949-55
17361218
Science. 2009 Jun 26;324(5935):1670-3
19556499
Nature. 2004 Nov 18;432(7015):396-401
15549107
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8
17210912
Cell Stem Cell. 2007 Nov;1(5):555-67
18371393
Nature. 2003 May 15;423(6937):255-60
12714970
Blood. 2008 Dec 15;112(13):4793-807
19064739
J Exp Med. 1996 Apr 1;183(4):1797-806
8666936
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5103-8
17372229
Cancer Cell. 2008 Feb;13(2):105-16
18242511
Nature. 2009 Dec 3;462(7273):595-601
19898493
N Engl J Med. 2004 Aug 12;351(7):657-67
15306667
Nature. 2008 Jan 17;451(7176):345-9
18202660
Cell Stem Cell. 2009 Jul 2;5(1):31-42
19570512
Nature. 2005 Dec 8;438(7069):820-7
16341007
Cancer Cell. 2008 Jun;13(6):483-95
18538732
Cancer Res. 2005 Dec 1;65(23):10946-51
16322242
Cancer Cell. 2007 Nov;12(5):467-78
17996650
Nature. 2009 Apr 9;458(7239):776-9
19169242
Cell Death Differ. 2008 Mar;15(3):504-14
18049477
Science. 2008 Dec 19;322(5909):1861-5
19095944
Cell Stem Cell. 2009 Feb 6;4(2):129-40
19200802
Nat Rev Cancer. 2008 Oct;8(10):755-68
18784658
Cancer Res. 2006 Aug 15;66(16):7843-8
16912155
Cell Stem Cell. 2007 Sep 13;1(3):313-23
18371365
Blood. 2004 Jun 1;103(11):4010-22
14982876
Leukemia. 2007 Dec;21(12):2559-61
17611557
Nature. 2007 Jan 4;445(7123):106-10
17122772
Cell Stem Cell. 2010 Mar 5;6(3):265-78
20207229
Blood. 2002 Jan 1;99(1):310-8
11756186
Cell Stem Cell. 2008 Dec 4;3(6):658-69
19041782
Nat Rev Drug Discov. 2009 Oct;8(10):806-23
19794444
Cancer Cell. 2002 Oct;2(4):289-300
12398893
Cancer Res. 2007 Feb 1;67(3):1030-7
17283135
Biochem Biophys Res Commun. 2007 Nov 23;363(3):578-83
17897629