Potential molecular therapeutic targets in cancer stem/progenitor cells: Are ATP-binding cassette membrane transporters appropriate targets to eliminate cancer-initiating cells?

Stem Cell Biology in Health and Disease

Volumn , Issue , 2009, Pages 385-421

  Mimeault, Murielle ^a   Batra, Surinder K ^a  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

ATP binding cassette transporters; Cancer stem progenitor cells; Cancer therapies; Combination therapies; Drug targets; Leukemias; Molecular targeting; Multidrug resistance; Oncogenic signaling elements; Solid tumors

Indexed keywords

EID: 84888200489     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-90-481-3040-5_17     Document Type: Chapter

References (284)

1. Wilson A, Trumpp A (2006) Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6:93-106
2. Arai F, Suda T (2007) Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche. Ann NY Acad Sci 1106:41-53
3. Rizo A, Vellenga E, de Haan G, et al. (2006) Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all stem cells need a niche? Hum Mol Genet 15 Spec No 2:R210-R219
4. Kim CF, Jackson EL, Woolfenden AE, et al. (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121:823-835
5. Mimeault M, Batra SK (2006) Recent advances on the significance of stem cells in tissue regeneration and cancer therapies. Stem Cells 24:2319-2345
6. Mimeault M, Hauke R, Batra SK (2007) Stem cells: a revolution in therapeutics-Recent advances on the stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies. Clin Pharmacol Ther 82:252-264
7. Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645-660
8. Mimeault M, Hauke R, Mehta PP, et al. (2007) Recent advances on cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. J Mol Cell Med 11:981-1011
9. Mimeault M, Batra SK (2008) Recent progress on tissue-resident adult stem cell biology and their therapeutic implications. Stem Cell Rev 4:27-49
10. Vaish M (2007) Mismatch repair deficiencies transforming stem cells into cancer stem cells and therapeutic implications. Mol Cancer 6:26
11. Mimeault M, Batra SK (2008) Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer. Gut 57:1456-1468
12. Mimeault M, Mehta PP, Hauke R, et al. (2008) Functions of normal and malignant prostatic stem/progenitor cells in tissue regeneration and cancer progression and novel targeting therapies. Endocr Rev 29:234-252
13. Sengupta A, Banerjee D, Chandra S, et al. (2007) Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression. Leukemia 21:949-955
14. Ponti D, Costa A, Zaffaroni N, et al. (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65:5506-5511
15. Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5: 738-743
16. MatsuiW, Huff CA,Wang Q, et al. (2004) Characterization of clonogenic multiple myeloma cells. Blood 103:2332-2336
17. Singh SK, Hawkins C, Clarke ID, et al. (2004) Identification of human brain tumour initiating cells. Nature 432:396-401
18. Fang D, Nguyen TK, Leishear K, et al. (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65:9328-9337
19. Wright MH, Calcagno AM, Salcido CD, et al. (2008) Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res 10:R10
20. Yang ZF, Ho DW, Ng MN, et al. (2008) Significance of CD90(+) cancer stem cells in human liver cancer. Cancer Cell 13:153-166
21. Hermann PC, Huber SL, Herrler T, et al. (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313-323
22. Ginestier C, Hur MH, Charafe-Jauffret E, et al. (2007) ALDH1 Is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555-567
23. Zhang S, Balch C, Chan MW, et al. (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68:4311-4320
24. Liu G, Yuan X, Zeng Z, et al. (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67
25. Fillmore CM, Kuperwasser C (2008) Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 10:R25
26. Schatton T, Murphy GF, Frank NY, et al. (2008) Identification of cells initiating human melanomas. Nature 451:345-349
27. Ricci-Vitiani L, Lombardi DG, Pilozzi E (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111-115
28. Wei C, GuominW, Yujun L, et al. (2007) Cancer stem-like cells in human prostate carcinoma cells DU145: The seeds of the cell line? Cancer Biol Ther 6:763-768.
29. Mimeault M, Batra SK (2007) Interplay of distinct growth factors during epithelialmesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies. Ann Oncol 18:1605-1619
30. Mimeault M, Batra SK (2007) Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications. Cancer Metastasis Rev 26:203-214
31. Mimeault M, Hauke R, Batra SK (2008) Recent advances on the molecular mechanisms involved in the drug resistance of cancer cells and novel targeting therapies. Clin Pharmacol Ther 83:673-691
32. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442-454
33. Brabletz T, Jung A, Spaderna S, et al. (2005) Opinion: migrating cancer stem cells-an integrated concept of malignant tumour progression. Nat Rev Cancer 5:744-749
34. Tso CL, Shintaku P, Chen J, et al. (2006) Primary glioblastomas express mesenchymal stemlike properties. Mol Cancer Res 4:607-619
35. Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275-284
36. Maitland NJ, Bryce SD, Stower MJ, et al. (2006) Prostate cancer stem cells: a target for new therapies. Ernst Schering Found Symp Proc 5:155-179
37. de Jonge-Peeters SD, Kuipers F, de Vries EG, et al. (2007) ABC transporter expression in hematopoietic stem cells and the role in AML drug resistance. Crit Rev Oncol Hematol 62:214-226
38. Zhang X, Komaki R,Wang L, et al. (2008) Treatment of radioresistant stem-like esophageal cancer cells by an apoptotic gene-armed, telomerase-specific oncolytic adenovirus. Clin Cancer Res 14:2813-2823
39. Todaro M, Alea MP, Di Stefano AB et al. (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1:389-402
40. Wang J, Guo LP, Chen LZ, et al. (2007) Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res 67:3716-3724
41. Hirschmann-Jax C, Foster AE, Wulf GG, et al. (2004) A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101: 14228-14233
42. Haraguchi N, Utsunomiya T, Inoue H, et al. (2006) Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 24:506-513
43. She JJ, Zhang PG, Wang ZM, et al. (2008) Identification of side population cells from bladder cancer cells by dyecycle violet staining. Cancer Biol Ther 7:1663-1668
44. Huang D, Gao Q, Guo L, et al. (2009) Isolation and identification of cancer stem-like cells in esophageal carcinoma cell lines. Stem Cells Dev 18: 465-473
45. Chiba T, Miyagi S, Saraya A, et al. (2008) The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. Cancer Res 68:7742-7749
46. Shi GM, Xu Y, Fan J, et al. (2008) Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials. J Cancer Res Clin Oncol 134:1155-1163
47. Sung JM, Cho HJ, Yi H, et al. (2008) Characterization of a stem cell population in lung cancer A549 cells. Biochem Biophys Res Commun 371:163-167
48. Friel AM, Sergent PA, Patnaude C, et al. (2008) Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells. Cell Cycle 7:242-249
49. Loebinger MR, Giangreco A, Groot KR, et al. (2008) Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade. Br J Cancer 98:380-387
50. Zhou J, Wang CY, Liu T, et al. (2008) Persistence of side population cells with high drug efflux capacity in pancreatic cancer. World J Gastroenterol 14:925-930
51. Eramo A, Lotti F, Sette G, et al. (2008) Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 15:504-514
52. Nicolis SK (2007) Cancer stem cells and "stemness" genes in neuro-oncology. Neurobiol Dis 25:217-229
53. Sato M, Shames DS, Gazdar AF, et al. (2007) A translational view of the molecular pathogenesis of lung cancer. J Thorac Oncol 2:327-343
54. Gray-Schopfer V, Wellbrock C, Marais R (2007) Melanoma biology and new targeted therapy. Nature 445:851-857
55. Ma S, Lee TK, Zheng BJ, et al. (2008) CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. Oncogene 27:1749-1758
56. Rich JN (2007) Cancer stem cells in radiation resistance. Cancer Res 67:8980-8984
57. KatohM(2007) Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. Stem Cell Rev 3:30-38
58. Glinsky GV (2008) "Stemness" genomics law governs clinical behavior of human cancer: implications for decision making in disease management. J Clin Oncol 26:2846-2853
59. Bao S, Wu Q, McLendon RE, et al. (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756-760
60. Mimeault M, Batra SK (2008) Targeting of cancer stem/progenitor cells plus stem cellbased therapies: the ultimate hope for treating and curing aggressive and recurrent cancers. Panminerva Med 50:3-18
61. Ho MM, Ng AV, Lam S, et al. (2007) Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 67:4827-4833
62. Salmaggi A, Boiardi A, GelatiM, et al. (2006) Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype. Glia 54:850-860
63. Frank NY, Margaryan A, Huang Y, et al. (2005) ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res 65:4320-4333
64. Kang MK, Kang SK (2007) Tumorigenesis of chemotherapeutic drug-resistant cancer stemlike cells in brain glioma. Stem Cells Dev 16:837-847
65. Johannessen TC, Bjerkvig R, Tysnes BB (2008) DNA repair and cancer stem-like cells - Potential partners in glioma drug resistance? Cancer Treat Rev 34:558-567
66. MatsuiW,Wang Q, Barber JP, et al. (2008) Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res 68:190-197
67. Dylla SJ, Beviglia L, Park IK, et al. (2008) Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS ONE 3:e2428
68. Shervington A, Lu C (2008) Expression of multidrug resistance genes in normal and cancer stem cells. Cancer Invest 26:535-542
69. Xu JX, Morii E, Liu Y, et al. (2007) High tolerance to apoptotic stimuli induced by serum depletion and ceramide in side-population cells: high expression of CD55 as a novel character for side-population. Exp Cell Res 313:1877-1885
70. Chen YC, Hsu HS, Chen YW, et al. (2008) Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS ONE 3:e2637
71. Widera D, Kaus A, Kaltschmidt C, et al. (2008) Neural stem cells, inflammation and NFkappaB: basic principle of maintenance and repair or origin of brain tumours? J Cell Mol Med 12:459-470
72. Birnie R, Bryce SD, Roome C, et al. (2008) Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions. Genome Biol 9:R83
73. Borst P, Elferink RO (2002) Mammalian ABC transporters in health and disease. Annu Rev Biochem 71:537-592
74. Mao Q, Unadkat JD (2005) Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J 7:E118-E133
75. Ozben T (2006) Mechanisms and strategies to overcome multiple drug resistance in cancer. FEBS Lett 580:2903-2909
76. Krishnamurthy P, Schuetz JD (2006) Role of ABCG2/BCRP in biology and medicine. Annu Rev Pharmacol Toxicol 46:381-410
77. Higgins CF (2007) Multiple molecular mechanisms for multidrug resistance transporters. Nature 446:749-757
78. Choudhuri S, Klaassen CD (2006) Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters. Int J Toxicol 25:231-259
79. Ho RH, Kim RB (2005) Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ther 78:260-277
80. Kaminski WE, Piehler A, Wenzel JJ (2006) ABC A-subfamily transporters: structure, function and disease. Biochim Biophys Acta 1762:510-524
81. Teodori E, Dei S, Martelli C, et al. (2006) The functions and structure of ABC transporters: implications for the design of new inhibitors of Pgp and MRP1 to control multidrug resistance (MDR). Curr Drug Targets 7:893-909
82. Deeley RG,Westlake C, Cole SP (2006) Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev 86:849-899
83. Szakacs G, Paterson JK, Ludwig JA, et al. (2006) Targeting multidrug resistance in cancer. Nat Rev Drug Discov 5:219-234
84. Gerk PM, Vore M (2002) Regulation of expression of the multidrug resistance-associated protein 2 (MRP2) and its role in drug disposition. J Pharmacol Exp Ther 302:407-415
85. Boumendjel A, Baubichon-Cortay H, Trompier D, et al. (2005) Anticancer multidrug resistance mediated by MRP1: recent advances in the discovery of reversal agents. Med Res Rev 25:453-472
86. Han B, Zhang JT (2004) Multidrug resistance in cancer chemotherapy and xenobiotic protection mediated by the half ATP-binding cassette transporter ABCG2. Curr Med Chem Anticancer Agents 4:31-42
87. Lin T, Islam O, Heese K (2006) ABC transporters, neural stem cells and neurogenesis-a different perspective. Cell Res 16:857-871
88. Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATPdependent transporters. Nat Rev Cancer 2:48-58
89. Efferth T, Gillet JP, Sauerbrey A, et al. (2006) Expression profiling of ATP-binding cassette transporters in childhood T-cell acute lymphoblastic leukemia. Mol Cancer Ther 5: 1986-1994
90. Steinbach D, Gillet JP, Sauerbrey A, et al. (2006) ABCA3 as a possible cause of drug resistance in childhood acute myeloid leukemia. Clin Cancer Res 12:4357-4363
91. Ahmed-Belkacem A, Pozza A, Macalou S, et al. (2006) Inhibitors of cancer cell multidrug resistance mediated by breast cancer resistance protein (BCRP/ABCG2). Anticancer Drugs 17:239-243
92. Allen JD, Brinkhuis RF, van Deemter L, et al. (2000) Extensive contribution of the multidrug transporters P-glycoprotein and Mrp1 to basal drug resistance. Cancer Res 60:5761-5766
93. Bessho Y, Oguri T, Achiwa H, et al. (2006) Role of ABCG2 as a biomarker for predicting resistance to CPT-11/SN-38 in lung cancer. Cancer Sci 97:192-198
94. Boonstra R, Timmer-Bosscha H, van Echten-Arends J, et al. (2004) Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation. Br J Cancer 90:2411-2417
95. Mack JT, Beljanski V, Tew KD, et al. (2006) The ATP-binding cassette transporter ABCA2 as a mediator of intracellular trafficking. Biomed Pharmacother 60:587-592
96. Hu C, Li H, Li J, et al. (2008) Analysis of ABCG2 expression and side population identifies intrinsic drug efflux in the HCC cell line MHCC-97L and its modulation by Akt signaling. Carcinogenesis 29:2289-2297
97. Challen GA, Little MH (2006) A side order of stem cells: the SP phenotype. Stem Cells 24:3-12
98. Bunting KD (2002) ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells 20:11-20
99. Chapuy B, Koch R, Radunski U, et al. (2008) Intracellular ABC transporter A3 confers multidrug resistance in leukemia cells by lysosomal drug sequestration. Leukemia 22: 1576-1586
100. Norwood K, Wang RY, Hirschmann-Jax C, et al. (2004) An in vivo propagated human acute myeloid leukemia expressing ABCA3. Leuk Res 28:295-299
101. Komuro H, Saihara R, Shinya M, et al. (2007) Identification of side population cells (stemlike cell population) in pediatric solid tumor cell lines. J Pediatr Surg 42:2040-2045
102. de Wolf C, Jansen R, Yamaguchi H, et al. (2008) Contribution of the drug transporter ABCG2 (breast cancer resistance protein) to resistance against anticancer nucleosides. Mol Cancer Ther 7:3092-3102
103. Ruefli AA, Tainton KM, Darcy PK, et al. (2002) P-glycoprotein inhibits caspase-8 activation but not formation of the death inducing signal complex (disc) following Fas ligation. Cell Death Differ 9:1266-1272
104. Turzanski J, Grundy M, Shang S, et al. (2005) P-glycoprotein is implicated in the inhibition of ceramide-induced apoptosis in TF-1 acute myeloid leukemia cells by modulation of the glucosylceramide synthase pathway. Exp Hematol 33:62-72
105. Nobili S, Landini I, Giglioni B, et al. (2006) Pharmacological strategies for overcoming multidrug resistance. Curr Drug Targets 7:861-879
106. Modok S, Mellor HR, Callaghan R (2006) Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer. Curr Opin Pharmacol 6:350-354
107. Wu H, Hait WN, Yang JM (2003) Small interfering RNA-induced suppression of MDR1 (P-glycoprotein) restores sensitivity to multidrug-resistant cancer cells. Cancer Res 63: 1515-1519
108. Haus-Cohen M, Assaraf YG, Binyamin L, et al. (2004) Disruption of P-glycoprotein anticancer drug efflux activity by a small recombinant single-chain Fv antibody fragment targeted to an extracellular epitope. Int J Cancer 109:750-758
109. Aouali N, Eddabra L, Macadre J, et al. (2005) Immunosuppressors and reversion of multidrug-resistance. Crit Rev Oncol Hematol 56:61-70
110. Cnubben NH,Wortelboer HM, van Zanden JJ, et al. (2005) Metabolism of ATP-binding cassette drug transporter inhibitors: complicating factor for multidrug resistance. Expert Opin Drug Metab Toxicol 1:219-232
111. Perez-Tomas R (2006) Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Curr Med Chem 13:1859-1876
112. Goda K, Fenyvesi F, Bacso Z, et al. (2007) Complete inhibition of P-glycoprotein by simultaneous treatment with a distinct class of modulators and the UIC2 monoclonal antibody. J Pharmacol Exp Ther 320:81-88
113. Saeki T, Nomizu T, Toi M, et al. (2007) Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin, and fluorouracil for patients with advanced or recurrent breast cancer. J Clin Oncol 25:411-417
114. Robert J (2004) MS-209 Schering. Curr Opin Investig Drugs 5:1340-1347
115. Dieras V, Bonneterre J, Laurence V, et al. (2005) Phase I combining a P-glycoprotein inhibitor, MS209, in combination with docetaxel in patients with advanced malignancies. Clin Cancer Res 11:6256-6260
116. Shareef MM, Brown B, Shajahan S, et al. (2008) Lack of P-glycoprotein expression by lowdose fractionated radiation results from loss of nuclear factor-kappaB and NF-Y activation in oral carcinoma cells. Mol Cancer Res 6:89-98
117. Takara K, Sakaeda T, Okumura K (2006) An update on overcoming MDR1-mediated multidrug resistance in cancer chemotherapy. Curr Pharm Des 12:273-286
118. Zhang S, Yang X, Morris ME (2004) Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Pharm Res 21:1263-1273
119. van Zanden JJ, Wortelboer HM, Bijlsma S, et al. (2005) Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and Biochem Pharmacol 69:699-708
120. Imai Y, Tsukahara S, Asada S, et al. (2004) Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res 64:4346-4352
121. Jordanides NE, Jorgensen HG, Holyoake TL, et al. (2006) Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate. Blood 108:1370-1373
122. Erlichman C, Boerner SA, Hallgren CG, et al. (2001) The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res 61:739-748
123. Ozvegy-Laczka C, Hegedus T, Varady G, et al. (2004) High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol 65: 1485-1495
124. Yanase K, Tsukahara S, Asada S, et al. (2004) Gefitinib reverses breast cancer resistance protein-mediated drug resistance. Mol Cancer Ther 3:1119-1125
125. Yang CH, Huang CJ, Yang CS, et al. (2005) Gefitinib reverses chemotherapy resistance in gefitinib-insensitive multidrug resistant cancer cells expressing ATP-binding cassette family protein. Cancer Res 65:6943-6949
126. Leggas M, Panetta JC, Zhuang Y, et al. (2006) Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer Res 66:4802-4807
127. Stewart CF, Leggas M, Schuetz JD, et al. (2004) Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice. Cancer Res 64:7491-7499
128. Nakamura Y, Oka M, Soda H, et al. (2005) Gefitinib ("Iressa", ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, reverses breast cancer resistance protein/ABCG2-mediated drug resistance. Cancer Res 65:1541-1546
129. Shen LZ, Hua YB, Yu XM, et al. (2005) Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo. World J Gastroenterol 11:1060-1064
130. Sugimoto Y, Tsukahara S, Imai Y, et al. (2003) Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther 2: 105-112
131. Shi Z, Peng XX, Kim IW, et al. (2007) Erlotinib (Tarceva, OSI-774) antagonizes ATPbinding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2-mediated drug resistance. Cancer Res 67:11012-11020
132. Chu TS, Chen JS, Lopez JP, et al. (2008) Imatinib-mediated inactivation of Akt regulates ABCG2 function in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 134:979-984
133. Jamieson CH, Ailles LE, Dylla SJ (2004) Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 351:657-667
134. Nakagawa R, Soh JW, Michie AM, et al. (2006) Subversion of protein kinase C alpha signaling in hematopoietic progenitor cells results in the generation of a B-cell chronic lymphocytic leukemia-like population in vivo. Cancer Res 66:527-534
135. Tallman MS (2007) Treatment of relapsed or refractory acute promyelocytic leukemia. Best Pract Res Clin Haematol 20:57-65
136. Zhou GB, Zhang J,Wang ZY, et al. (2007) Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy. Philos Trans R Soc Lond B Biol Sci 362:959-971
137. Martinez-Jaramillo G, Vela-Ojeda J, Sanchez-Valle E, et al. (2007) In vitro functional alterations in the hematopoietic system of adult patients with acute lymphoblastic leukemia. Leuk Res 31:83-89
138. Chambers SM, Goodell MA (2007) Hematopoietic stem cell aging: wrinkles in stem cell potential. Stem Cell Rev 3:201-211
139. Rossi DJ, Bryder D, Weissman IL (2007) Hematopoietic stem cell aging: Mechanism and consequence. Exp Gerontol 42:385-390
140. Chumsri S, Matsui W, Burger AM (2007) Therapeutic implications of leukemic stem cell pathways. Clin Cancer Res 13:6549-6554
141. Jorgensen HG, Holyoake TL (2007) Characterization of cancer stem cells in chronic myeloid leukaemia. Biochem Soc Trans 35:1347-1351
142. Suarez L, Vidriales MB, Moreno MJ, et al. (2005) Differences in anti-apoptotic and multidrug resistance phenotypes in elderly and young acute myeloid leukemia patients are related to the maturation of blast cells. Haematologica 90:54-59
143. Tallman MS, Gilliland DG, Rowe JM (2005) Drug therapy for acute myeloid leukemia. Blood 106:1154-1163
144. Misaghian N, Ligresti G, Steelman LS, et al. (2008) Targeting the leukemic stem cell: the Holy Grail of leukemia therapy. Leukemia
145. Sell S (2005) Leukemia: stem cells, maturation arrest, and differentiation therapy. Stem Cell Rev 1:197-205
146. Mehta K, Ocanas L, Malavasi F, et al. (2004) Retinoic acid-induced CD38 antigen as a target for immunotoxin-mediated killing of leukemia cells. Mol Cancer Ther 3:345-352
147. Mathieu J, Besancon F (2006) Arsenic trioxide represses NF-kappaB activation and increases apoptosis in ATRA-treated APL cells. Ann NY Acad Sci 1090:203-208
148. Stevenson GT (2006) CD38 as a therapeutic target. Mol Med 12:345-346
149. Arora A, Scholar EM (2005) Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther 315:971-979
150. Zheng X, Seshire A, Ruster B, et al. (2007) Arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha-positive leukemic stem cells. Haematologica 92:323-331
151. Miller WH, Jr., Schipper HM, Lee JS, et al. (2002) Mechanisms of action of arsenic trioxide. Cancer Res 62:3893-3903
152. Small D (2006) FLT3 mutations: biology and treatment. Hematology Am Soc Hematol Educ Program 178-184
153. Hauswirth AW, Florian S, Printz D, et al. (2007) Expression of the target receptor CD33 in CD34+/CD38-/CD123+ AML stem cells. Eur J Clin Invest 37:73-82
154. Larson RA, Sievers EL, Stadtmauer EA, et al. (2005) Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 104:1442-1452
155. Roman E, Cooney E, Harrison L, et al. (2005) Preliminary results of the safety of immunotherapy with gemtuzumab ozogamicin following reduced intensity allogeneic stem cell transplant in children with CD33+ acute myeloid leukemia. Clin Cancer Res 11: 7164s-7170s
156. Bornhauser M, Illmer T, Oelschlaegel U, et al. (2008) Gemtuzumab ozogamicin as part of reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in patients with relapsed acute myeloid leukemia. Clin Cancer Res 14:5585-5593
157. Candoni A, Martinelli G, Toffoletti E, et al. (2008) Gemtuzumab- ozogamicin in combination with fludarabine, cytarabine, idarubicin (FLAI-GO) as induction therapy in CD33-positive AML patients younger than 65 years. Leuk Res 32:1800-1808
158. Mulford D (2008) Antibody therapy for acute myeloid leukemia. Semin Hematol 45: 104-109
159. Balduzzi A, Rossi V, Corral L, et al. (2003) Molecular remission induced by gemtuzumab ozogamicin associated with donor lymphocyte infusions in t(4;11) acute lymphoblastic leukemia relapsed after transplantation. Leukemia 17:2247-2248
160. Chevallier P, Mahe B, Garand R, et al. (2008) Combination of chemotherapy and gemtuzumab ozogamicin in adult Philadelphia positive acute lymphoblastic leukemia patient harboring CD33 expression. Int J Hematol 88:209-211
161. Moore J, Seiter K, Kolitz J, et al. (2006) A Phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse. Leuk Res 30:777-783
162. Kersemans V, Cornelissen B, Minden MD, et al. (2008) Drug-resistant AML cells and primary AML specimens are killed by 111In-anti-CD33 monoclonal antibodies modified with nuclear localizing peptide sequences. J Nucl Med 49:1546-1554
163. de Figueiredo-Pontes LL, Pintao MC, Oliveira LC, et al. (2008) Determination of Pglycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia. Cytometry B Clin Cytom 74:163-168
164. Damiani D, Tiribelli M, Raspadori D, et al. (2007) The role of MDR-related proteins in the prognosis of adult acute myeloid leukaemia (AML) with normal karyotype. Hematol Oncol 25:38-43
165. Huh HJ, Park CJ, Jang S, et al. (2006) Prognostic significance of multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression in acute leukemia. J Korean Med Sci 21:253-258
166. Jordan CT (2002) Unique molecular and cellular features of acute myelogenous leukemia stem cells. Leukemia 16:559-562
167. Wulf GG, Wang RY, Kuehnle I, et al. (2001) A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 98:1166-1173
168. Ho MM, Hogge DE, Ling V (2008) MDR1 and BCRP1 expression in leukemic progenitors correlates with chemotherapy response in acute myeloid leukemia. Exp Hematol 36: 433-442
169. List AF, Kopecky KJ, Willman CL, et al. (2001) Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood 98:3212-3220
170. Greenberg PL, Lee SJ, Advani R, et al. (2004) Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol 22: 1078-1086
171. Raaijmakers MH, de Grouw EP, Heuver LH, et al. (2005) Breast cancer resistance protein in drug resistance of primitive CD34+38- cells in acute myeloid leukemia. Clin Cancer Res 11:2436-2444
172. Burger H, Nooter K (2004) Pharmacokinetic resistance to imatinib mesylate: role of the ABC drug pumps ABCG2 (BCRP) and ABCB1 (MDR1) in the oral bioavailability of imatinib. Cell Cycle 3:1502-1505
173. Jiang X, Zhao Y, Smith C, et al. (2007) Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies. Leukemia 21:926-935
174. Copland M, Hamilton A, Elrick LJ, et al. (2006) Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 107:4532-4539
175. Mughal T, Goldman JM (2007) Optimal management of patients with newly diagnosed chronic phase chronic myeloid leukemia in 2007. Clin Lymphoma Myeloma 7 Suppl 3:S95-S101
176. Hu Y, Swerdlow S, Duffy TM, et al. (2006) Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. Proc Natl Acad Sci USA 103:16870-16875
177. Zhou LL, Zhao Y, Ringrose A, et al. (2008) AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells. J Exp Med 205:2657-2671
178. Copland M, Pellicano F, Richmond L, et al. (2008) BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Blood 111:2843-2853
179. Angstreich GR, Matsui W, Huff CA, et al. (2005) Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors. Br J Haematol 130:373-381
180. White DL, Saunders VA, Dang P, et al. (2006) OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib. Blood 108:697-704
181. Kuroda J, Puthalakath H, Cragg MS, et al. (2006) Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc Natl Acad Sci USA 103:14907-14912
182. Holtz M, Forman SJ, Bhatia R (2007) Growth factor stimulation reduces residual quiescent chronic myelogenous leukemia progenitors remaining after imatinib treatment. Cancer Res 67:1113-1120
183. Giannoudis A, Davies A, Lucas CM, et al. (2008) Effective dasatinib uptake may occur without human organic cation transporter 1 (hOCT1): implications for the treatment of imatinib-resistant chronic myeloid leukemia. Blood 112:3348-3354
184. Dulucq S, Bouchet S, Turcq B, et al. (2008) Multidrug resistance gene
185. Stromskaya TP, Rybalkina EY, Kruglov SS, et al. (2008) Role of P-glycoprotein in evolution of populations of chronic myeloid leukemia cells treated with imatinib. Biochemistry (Mosc) 73:29-37
186. Heaney NB, Holyoake TL (2007) Therapeutic targets in chronic myeloid leukaemia. Hematol Oncol 25:66-75
187. Brendel C, Scharenberg C, Dohse M, et al. (2007) Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells. Leukemia 21:1267-1275
188. MauroMJ (2006) Defining and managing imatinib resistance. Hematology Am Soc Hematol Educ Program 219-225
189. Guzman ML, Li X, Corbett CA, et al. (2007) Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8). Blood 110:4436-4444
190. Barfield RC, Hale GA, Burnette K, et al. (2007) Autologous transplantation of CD133 selected hematopoietic progenitor cells for treatment of relapsed acute lymphoblastic leukemia. Pediatr Blood Cancer 48:349-353
191. Ringden O (2007) Immunotherapy by allogeneic stem cell transplantation. Adv Cancer Res 97C:25-60
192. Chen KG, Szakacs G, Annereau JP, et al. (2005) Principal expression of two mRNA isoforms (ABCB 5alpha and ABCB 5beta) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes. Pigment Cell Res 18:102-112
193. Dou J, Pan M,Wen P, et al. (2007) Isolation and identification of cancer stem-like cells from murine melanoma cell lines. Cell Mol Immunol 4:467-472
194. Monzani E, Facchetti F, Galmozzi E, et al. (2007) Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer 43:935-946
195. Keshet GI, Goldstein I, Itzhaki O, et al. (2008) MDR1 expression identifies human melanoma stem cells. Biochem Biophys Res Commun 368:930-936
196. Hadnagy A, Gaboury L, Beaulieu R, et al. (2006) SP analysis may be used to identify cancer stem cell populations. Exp Cell Res 312:3701-3710
197. Klein WM, Wu BP, Zhao S, et al. (2007) Increased expression of stem cell markers in malignant melanoma. Mod Pathol 20:102-107
198. Tchernev G, Orfanos CE (2007) Downregulation of cell cycle modulators p21, p27, p53, Rb and proapoptotic Bcl-2-related proteins Bax and Bak in cutaneous melanoma is associated with worse patient prognosis: preliminary findings. J Cutan Pathol 34:247-256
199. Pinnix CC, Herlyn M (2007) The many faces of Notch signaling in skin-derived cells. Pigment Cell Res 20:458-465
200. Dahl C, Guldberg P (2007) The genome and epigenome of malignant melanoma. APMIS 115:1161-1176
201. Pons M, Quintanilla M (2006) Molecular biology of malignant melanoma and other cutaneous tumors. Clin Transl Oncol 8:466-474
202. Strizzi L, Abbott DE, Salomon DS, et al. (2008) Potential for cripto-1 in defining stem cell-like characteristics in human malignant melanoma. Cell Cycle 7:1931-1935
203. Curtin JA, Busam K, Pinkel D, et al. (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24:4340-4346
204. Ahrens T, Sleeman JP, Schempp CM, et al. (2001) Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid. Oncogene 20:3399-3408
205. Yokoyama S, Feige E, Poling LL, et al. (2008) Pharmacologic suppression of MITF expression via HDAC inhibitors in the melanocyte lineage. Pigment Cell Melanoma Res 21:457-463
206. Tsao H, Atkins MB, Sober AJ (2004) Management of cutaneous melanoma. N Engl J Med 351:998-1012
207. den Brok MH, Nierkens S, Figdor CG, et al. (2005) Dendritic cells: tools and targets for antitumor vaccination. Expert Rev Vaccines 4:699-710
208. Sigalotti L, Covre A, Zabierowski S, et al. (2008) Cancer testis antigens in human melanoma stem cells: Expression, distribution, and methylation status. J Cell Physiol 215:287-291
209. Aboody KS, Bush RA, Garcia E, et al. (2006) Development of a tumor-selective approach to treat metastatic cancer. PLoS ONE 1:e23
210. Taylor MD, Poppleton H, Fuller C, et al. (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323-335
211. Singh SK, Clarke ID, Terasaki M, et al. (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821-5828
212. Hemmati HD, Nakano I, Lazareff JA, et al. (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100:15178-15183
213. Yuan X, Curtin J, Xiong Y, et al. (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23:9392-9400
214. Galli R, Binda E, Orfanelli U, et al. (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011-7021
215. Sanai N, varez-Buylla A, Berger MS (2005) Neural stem cells and the origin of gliomas. N Engl J Med 353:811-822
216. Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6: 425-436
217. Sharma MK, Mansur DB, Reifenberger G, et al. (2007) Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res 67:890-900
218. Mao Y, Zhou L, Zhu W, et al. (2007) Proliferative status of tumor stem cells may be correlated with malignancy grade of human astrocytomas. Front Biosci 12:2252-2259
219. Ross RA, Spengler BA (2007) Human neuroblastoma stem cells. Semin Cancer Biol 17: 241-247
220. Baehring JM (2005) An update on oligodendroglial neoplasms. Curr Opin Neurol 18: 639-644
221. Yu SC, Ping YF, Yi L, et al. (2008) Isolation and characterization of cancer stem cells from a human glioblastoma cell line U87. Cancer Lett 265:124-134
222. Salmaggi A, Boiardi A, GelatiM, et al. (2006) Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype. Glia 54:850-860
223. Beier D, Hau P, Proescholdt M, et al. (2007) CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res 67:4010-4015
224. Kondo T, Setoguchi T, Taga T (2004) Persistence of a small subpopulation of cancer stemlike cells in the C6 glioma cell line. Proc Natl Acad Sci USA 101:781-786
225. Beachy PA, Karhadkar SS, Berman DM (2004) Tissue repair and stem cell renewal in carcinogenesis. Nature 432:324-331
226. Galderisi U, Cipollaro M, Giordano A (2006) Stem cells and brain cancer. Cell Death Differ 13:5-11
227. Thompson MC, Fuller C, Hogg TL, et al. (2006) Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24:1924-1931
228. Rubin JB, Kung AL, Klein RS, et al. (2003) A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci USA 100: 13513-13518
229. Calabrese C, Poppleton H, Kocak M, et al. (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11:69-82
230. Annabi B, Rojas-Sutterlin S, Laflamme C, et al. (2008) Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res 6:907-916
231. Jin F, Zhao L, Zhao HY, et al. (2008) Comparison between cells and cancer stem-like cells isolated from glioblastoma and astrocytoma on expression of anti-apoptotic and multidrug resistance-associated protein genes. Neuroscience 154:541-550
232. Avramova B, Jordanova M, Michailov G, et al. (2006) Myeloablative chemotherapy with autologous peripheral blood stem cell transplantation in patients with poor-prognosis solid tumors - Bulgarian experience. J BUON 11:433-438
233. Valteau-Couanet D, Minard V (2007) Poor prognosis childhood cancers. Rev Prat 57: 1087-1091
234. Lu C, Shervington A (2008) Chemoresistance in gliomas. Mol Cell Biochem 312:71-80
235. Gilg AG, Tye SL, Tolliver LB, et al. (2008) Targeting hyaluronan interactions in malignant gliomas and their drug-resistant multipotent progenitors. Clin Cancer Res 14: 1804-1813
236. Fan X, Matsui W, Khaki L, et al. (2006) Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res 66:7445-7452
237. Clement V, Sanchez P, de Tribolet N, et al. (2007) HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17: 165-172
238. Ehtesham M, Kabos P, Kabosova A, et al. (2002) The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma. Cancer Res 62:5657-5663
239. Ehtesham M, Kabos P, Gutierrez MA, et al. (2002) Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 62:7170-7174
240. Mapara KY, Stevenson CB, Thompson RC, et al. (2007) Stem cells as vehicles for the treatment of brain cancer. Neurosurg Clin N Am 18:71-80, ix
241. Miller SJ, Lavker RM, Sun TT (2005) Interpreting epithelial cancer biology in the context of stem cells: tumor properties and therapeutic implications. Biochim Biophys Acta 1756: 25-52
242. Al-Hajj M, Clarke MF (2004) Self-renewal and solid tumor stem cells. Oncogene 23: 7274-7282
243. Mimeault M, Mehta PP, Hauke R, et al. (2007) Improvement of cytotoxic effects of mitoxantrone on hormone-refractory metastatic prostate cancer cells by co-targeting epidermal growth factor receptor and hedgehog signaling cascades. Growth Factors 25: 400-416
244. Prince ME, Sivanandan R, Kaczorowski A, et al. (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 104:973-978
245. Mitsutake N, Iwao A, Nagai K, et al. (2007) Characterization of side population in thyroid cancer cell lines: cancer stem-like cells are enriched partly but not exclusively. Endocrinology 148:1797-1803
246. Bapat SA, Mali AM, Koppikar CB, et al. (2005) Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 65:3025-3029
247. Mimeault M, Batra SK (2008) Recent advances on the development of novel anti-cancer drugs targeting cancer stem/progenitor cells. Drug Develop Res 69: 415-430
248. Liu S, Dontu G, Mantle ID, et al. (2006) Hedgehog signaling and Bmi-1 regulate selfrenewal of normal and malignant human mammary stem cells. Cancer Res 66:6063-6071
249. Chen JS, Pardo FS, Wang-Rodriguez J, et al. (2006) EGFR regulates the side population in head and neck squamous cell carcinoma. Laryngoscope 116:401-406
250. Karhadkar SS, Bova GS, Abdallah N, et al. (2004) Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 431:707-712
251. Feldmann G, Dhara S, Fendrich V, et al. (2007) Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 67:2187-2196
252. Rubin LL, de Sauvage FJ (2006) Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov 5:1026-1033
253. Villanueva A, Newell P, Chiang DY, et al. (2007) Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis 27:55-76
254. Kucia M, Reca R, Miekus K, et al. (2005) Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 23:879-894
255. Misra S, Toole BP, Ghatak S (2006) Hyaluronan constitutively regulates activation of multiple receptor tyrosine kinases in epithelial and carcinoma cells. J Biol Chem 281: 34936-34941
256. Ghatak S, Misra S, Toole BP (2002) Hyaluronan oligosaccharides inhibit anchorageindependent growth of tumor cells by suppressing the phosphoinositide 3-kinase/Akt cell survival pathway. J Biol Chem 277:38013-38020
257. Bourguignon LY, Peyrollier K, Xia W, et al. (2008) Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells. J Biol Chem 283:17635-17651
258. Sims-Mourtada J, Izzo JG, Ajani J, et al. (2007) Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport. Oncogene 26:5674-5679
259. Liang Z, Wu T, Lou H, et al. (2004) Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4. Cancer Res 64:4302-4308
260. Zhou J, Zhang H, Gu P, et al. (2007) NF-kappaB pathway inhibitors preferentially inhibit breast cancer stem-like cells. Breast Cancer Res Treat 29:909-912
261. Zhou J,Wulfkuhle J, Zhang H, et al. (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci USA 104:16158-16163
262. Segui B, Andrieu-Abadie N, Jaffrezou JP, et al. (2006) Sphingolipids asmodulators of cancer cell death: potential therapeutic targets. Biochim Biophys Acta 1758:2104-2120
263. Deng Y, Chang S (2007) Role of telomeres and telomerase in genomic instability, senescence and cancer. Lab Invest 87:1071-1076
264. Harley CB (2008) Telomerase and cancer therapeutics. Nat Rev Cancer 8:167-179
265. Shay JW, Keith WN (2008) Targeting telomerase for cancer therapeutics. Br J Cancer 98:677-683
266. Jackson SR, Zhu CH, Paulson V, et al. (2007) Antiadhesive effects of GRN163L- an oligonucleotide N3-P5 thio-phosphoramidate targeting telomerase. Cancer Res 67: 1121-1129
267. Murofushi Y, Nagano S, Kamizono J, et al. (2006) Cell cycle-specific changes in hTERT promoter activity in normal and cancerous cells in adenoviral gene therapy: a promising implication of telomerase-dependent targeted cancer gene therapy. Int J Oncol 29:681-688
268. Bauerschmitz GJ, Ranki T, Kangasniemi L, et al. (2008) Tissue-specific promoters active in CD44+CD24-/low breast cancer cells. Cancer Res 68:5533-5539
269. Shay JW, Wright WE (2006) Telomerase therapeutics for cancer: challenges and new directions. Nat Rev Drug Discov 5:577-584
270. Vonderheide RH, Domchek SM, Schultze JL, et al. (2004) Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res 10:828-839
271. Brunsvig PF, Aamdal S, Gjertsen MK, et al. (2006) Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer. Cancer Immunol Immunother 55:1553-1564
272. Su Z, Dannull J, Yang BK, Dahm P, et al. (2005) Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J Immunol 174:3798-3807
273. Mimeault M (2002) New advances on structural and biological functions of ceramide in apoptotic/necrotic cell death and cancer. FEBS Lett 530:9-16
274. Sell S (2004) Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51:1-28
275. Sano T, Kagawa M, Okuno M, et al. (2005) Prevention of rat hepatocarcinogenesis by acyclic retinoid is accompanied by reduction in emergence of both TGF-alpha-expressing oval-like cells and activated hepatic stellate cells. Nutr Cancer 51:197-206
276. Massard C, Deutsch E, Soria JC (2006) Tumour stem cell-targeted treatment: elimination or differentiation. Ann Oncol 17:1620-1624
277. Perabo FG, Muller SC (2006) New agents for treatment of advanced transitional cell carcinoma. Ann Oncol 18:835-843
278. Moserle L, Indraccolo S, Ghisi M, et al. (2008) The side population of ovarian cancer cells is a primary target of IFN-alpha antitumor effects. Cancer Res 68:5658-5668
279. Schrama D, Reisfeld RA, Becker JC, et al. (2006) Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov 5:147-159
280. Schatzlein AG (2006) Delivering cancer stem cell therapies - a role for nanomedicines? Eur J Cancer 42:1309-1315
281. Muller FJ, Snyder EY, Loring JF, et al. (2006) Gene therapy: can neural stem cells deliver? Nat Rev Neurosci 7:75-84
282. Liu Y, LuWL, Guo J, et al. (2008) A potential target associated with both cancer and cancer stem cells: a combination therapy for eradication of breast cancer using vinorelbine stealthy liposomes plus parthenolide stealthy liposomes. J Control Release 129:18-25
283. Thorne SH (2007) Strategies to achieve systemic delivery of therapeutic cells and microbes to tumors. Expert Opin Biol Ther 7:41-51
284. Perillo A, Ferrandina G, Pierelli L, et al. (2005) Stem cell-based treatments for gynecological solid tumors. Eur Rev Med Pharmacol Sci 9:93-102