title: Cancer stem cells: perspectives for therapeutic targeting.
abstract: Cells with "stemness" and tumor-initiating properties have been isolated from both hematological and solid tumors. These cells denominated as cancer stem cells (CSCs), representing rare populations within tumors, have the ability to metastasize and are resistant to standard therapies and immunotherapy. Heterogeneity and plasticity in the phenotype of CSCs have been described in relation to their tissue origin. Few definitive markers have been isolated for CSCs from human solid tumors, limiting their usage for in vivo identification of these cells. Nevertheless, progress in the emerging CSCs concept has been achieved gaining, at least for some type of tumors, their biological and immunological characterization. The recent identification of molecules and signaling pathways that are up-regulated or aberrantly induced in CSCs allowed the development of small agents for specifically targeting of CSCs. A general low immunogenic profile has been reported for CSCs with, in some cases, the identification of the mechanisms responsible of the impairment of cell-mediated immune responses. These concepts are discussed in the context of this review. Although CSCs still need to be fully characterized, potential candidate markers and/or signaling pathways, to be exploited for the design of novel CSC-targeting therapeutic strategies, are described in this review.
authors.affiliation: Unit of Immuno-biotherapy of Melanoma and Solid Tumors, San Raffaele Foundation Centre, Milan, Italy, crimaccalli@gmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Maccalli
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
references.citation: Cancer Cell. 2006 May;9(5):391-403
references.pmid: 16697959
references.citation: Nat Rev Cancer. 2011 Apr;11(4):254-67
references.pmid: 21390059
references.citation: Clin Cancer Res. 2012 Jul 1;18(13):3495-8
references.pmid: 22711710
references.citation: Int J Gynecol Cancer. 2013 Oct;23(8):1367-75
references.pmid: 24257550
references.citation: Cancer Res. 2008 Jun 1;68(11):4022-5
references.pmid: 18519657
references.citation: Cancer J. 2012 Mar-Apr;18(2):153-9
references.pmid: 22453017
references.citation: Cancer Res. 2010 Jan 15;70(2):697-708
references.pmid: 20068175
references.citation: Nature. 2006 Dec 7;444(7120):756-60
references.pmid: 17051156
references.citation: Breast Cancer Res. 2011 Sep 14;13(5):R88
references.pmid: 21914219
references.citation: Clin Cancer Res. 2011 Aug 1;17(15):4942-7
references.pmid: 21622723
references.citation: Cancer Immunol Immunother. 2012 Aug;61(8):1255-68
references.pmid: 22270714
references.citation: Gastroenterology. 2011 Jan;140(1):297-309
references.pmid: 20951698
references.citation: Cancer Lett. 2013 May 28;332(2):374-82
references.pmid: 21315505
references.citation: Cell. 2008 May 16;133(4):704-15
references.pmid: 18485877
references.citation: Breast Cancer Res Treat. 2012 Jun;133(2):437-45
references.pmid: 21915634
references.citation: J Neurosci Res. 2009 Aug 1;87(10):2264-72
references.pmid: 19301423
references.citation: Cancer Res. 2010 Nov 1;70(21):8874-85
references.pmid: 20959469
references.citation: J Neuroimmunol. 2012 Sep 15;250(1-2):27-34
references.pmid: 22688424
references.citation: Cell Stem Cell. 2009 Aug 7;5(2):168-77
references.pmid: 19664991
references.citation: Cell Stem Cell. 2014 Mar 6;14(3):342-56
references.pmid: 24607406
references.citation: Curr Drug Deliv. 2012 Jan;9(1):5-16
references.pmid: 22023212
references.citation: Cell. 2009 Aug 21;138(4):645-659
references.pmid: 19682730
references.citation: Mol Cancer Ther. 2014 Feb;13(2):386-98
references.pmid: 24344235
references.citation: Eur J Cancer. 2014 Feb;50(3):649-55
references.pmid: 24333096
references.citation: Nature. 2006 Dec 7;444(7120):761-5
references.pmid: 17151667
references.citation: Cell Stem Cell. 2010 May 7;6(5):421-32
references.pmid: 20452317
references.citation: Stem Cells. 2012 Sep;30(9):1819-30
references.pmid: 22753241
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8
references.pmid: 12629218
references.citation: Onco Targets Ther. 2013 Sep 04;6:1207-20
references.pmid: 24043946
references.citation: Cancer Res. 2005 Dec 15;65(24):11469-77
references.pmid: 16357155
references.citation: Clin Cancer Res. 2010 Aug 1;16(15):3851-9
references.pmid: 20534737
references.citation: Nature. 2007 Jan 4;445(7123):111-5
references.pmid: 17122771
references.citation: Neoplasia. 2009 Aug;11(8):743-52
references.pmid: 19649204
references.citation: J Immunol. 2013 Mar 1;190(5):2381-90
references.pmid: 23345327
references.citation: Cell Death Differ. 2012 May;19(5):768-78
references.pmid: 22117197
references.citation: Nat Med. 1997 Jul;3(7):730-7
references.pmid: 9212098
references.citation: Nat Rev Clin Oncol. 2012 May 08;9(6):314-26
references.pmid: 22566105
references.citation: Ann N Y Acad Sci. 2009 Sep;1176:154-69
references.pmid: 19796244
references.citation: Cancer Cell. 2012 Dec 11;22(6):765-80
references.pmid: 23238013
references.citation: Nat Med. 2011 Mar;17(3):313-9
references.pmid: 21386835
references.citation: Cell Stem Cell. 2007 Nov;1(5):555-67
references.pmid: 18371393
references.citation: Blood. 2008 Dec 15;112(13):4793-807
references.pmid: 19064739
references.citation: Nanomedicine. 2011 Feb;7(1):69-79
references.pmid: 20620237
references.citation: Cancer Res. 2012 Dec 15;72(24):6338-43
references.pmid: 23222300
references.citation: Sci Rep. 2013;3:2298
references.pmid: 23892388
references.citation: Clin Cancer Res. 2010 Feb 1;16(3):800-13
references.pmid: 20103663
references.citation: Biochem Biophys Res Commun. 2012 Oct 19;427(2):373-8
references.pmid: 22995296
references.citation: Cancer Immunol Immunother. 2009 May;58(5):801-8
references.pmid: 19089424
references.citation: Cell. 2006 Mar 24;124(6):1111-5
references.pmid: 16564000
references.citation: Nature. 2005 Jun 23;435(7045):1126-30
references.pmid: 15973414
references.citation: Cancer Treat Rev. 2013 Aug;39(5):525-33
references.pmid: 23207059
references.citation: J Immunol. 2014 Jan 1;192(1):523-32
references.pmid: 24277698
references.citation: PLoS One. 2010 Jun 07;5(6):e10974
references.pmid: 20539758
references.citation: J Natl Cancer Inst. 2006 Dec 20;98(24):1755-7
references.pmid: 17179471
references.citation: Nat Rev Cancer. 2012 Mar 22;12(4):252-64
references.pmid: 22437870
references.citation: FASEB J. 2010 Nov;24(11):4291-301
references.pmid: 20566622
references.citation: Nature. 2011 Dec 07;481(7379):85-9
references.pmid: 22158103
references.citation: Cell Death Differ. 2012 Oct;19(10):1644-54
references.pmid: 22539003
references.citation: Stem Cells. 2012 Nov;30(11):2378-86
references.pmid: 22969042
references.citation: Cell Death Differ. 2008 Sep;15(9):1491-8
references.pmid: 18497759
references.citation: Clin Cancer Res. 2010 Jan 15;16(2):461-73
references.pmid: 20068105
references.citation: Blood. 1999 Oct 1;94(7):2225-9
references.pmid: 10498592