Understanding and targeting cancer stem cells: Therapeutic implications and challenges

Acta Pharmacologica Sinica

Volumn 34, Issue 6, 2013, Pages 732-740

  Chen, Ke ^a   Huang, Ying Hui ^b   Chen, Ji Long ^a,c  

^a INSTITUTE OF MICROBIOLOGY   (China)

^b JILIN UNIVERSITY   (China)

^c FUJIAN AGRICULTURE AND FORESTRY UNIVERSITY   (China)

Author keywords

ATP binding cassette transporter; biomarker; cancer; leukemia; signaling pathway; stem cell; tumor microenvironment

Indexed keywords

ABC TRANSPORTER; BETA CATENIN; CD133 ANTIGEN; CELL SURFACE MARKER; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; JANUS KINASE; NOTCH RECEPTOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN BCL 2; SONIC HEDGEHOG PROTEIN; STAT PROTEIN; SURVIVIN; WNT PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; APOPTOSIS; BRAIN CANCER; BREAST CANCER; CANCER STEM CELL; CELL HETEROGENEITY; CELL IMMORTALIZATION; CELL POPULATION; CELL RENEWAL; CHRONIC MYELOID LEUKEMIA; CLONAL EVOLUTION; COLON CANCER; DISEASE ERADICATION; FLUORESCENCE ACTIVATED CELL SORTING; HEAD AND NECK CANCER; HUMAN; LIVER CANCER; LUNG CANCER; MELANOMA; MOLECULARLY TARGETED THERAPY; MULTIPLE MYELOMA; PANCREAS CANCER; PHENOTYPE; PROSTATE CANCER; REVIEW; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL DIFFERENTIATION; DISEASE PROGRESSION; DRUG DESIGN; DRUG RESISTANCE, NEOPLASM; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM METASTASIS; NEOPLASM RECURRENCE, LOCAL; NEOPLASMS; NEOPLASTIC STEM CELLS;

EID: 84881453720     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2013.27     Document Type: Review

References (102)

1. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105-11.
2. Bruce WR, Van Der Gaag H. A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature 1963; 199: 79-80.
3. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3: 730-7.
4. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100: 3983-8.
5. Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005; 121: 823-35.
6. O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445: 106-10.
7. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005; 65: 10946-51.
8. Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci USA 2006; 103: 11154-9.
9. Piccirillo SGM, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 2006; 444: 761-5.
10. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 2005; 65: 9328-37.
11. Tang DG. Understanding cancer stem cell heterogeneity and plasticity. Cell Res 2012; 22: 457-72.
12. Campbell LL, Polyak K. Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle 2007; 6: 2332-8.
13. Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta 2010; 1805: 105-17.
14. Anderson K, Lutz C, van Delft FW, Bateman CM, Guo Y, Colman SM, et al. Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature 2011; 469: 356-61.
15. Notta F, Mullighan CG, Wang JCY, Poeppl A, Doulatov S, Phillips LA, et al. Evolution of human BCR-ABL1 lymphoblastic leukaemia-initiating cells. Nature 2011; 469: 362-7.
16. Kreso A, O'Brien CA, van Galen P, Gan OI, Notta F, Brown AMK, et al. Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science 2013; 339: 543-8.
17. Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annu Rev Med 2007; 58: 267-84.
18. Guzman ML, Jordan CT. Considerations for targeting malignant stem cells in leukemia. Cancer Control 2004; 11: 97-104.
19. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature 2004; 432: 396-401.
20. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007; 1: 555-67.
21. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 2008; 13: 153-66.
22. Rountree CB, Senadheera S, Mato JM, Crooks GM, Lu SC. Expansion of liver cancer stem cells during aging in methionine adenosyltransferase 1A-deficient mice. Hepatology 2008; 47: 1288-97.
23. Gilbert CA, Ross AH. Cancer stem cells: cell culture, markers, and targets for new therapies. J Cell Biochem 2009; 108: 1031-8.
24. Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ 2007; 15: 504-14.
25. Ho MM, Ng AV, Lam S, Hung JY. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res 2007; 67: 4827-33.
26. Dalerba P, Dylla SJ, Park I-K, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 2007; 104: 10158-63.
27. Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci USA 2010; 107: 3722-7.
28. O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445: 106-10.
29. Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, et al. Characterization of clonogenic multiple myeloma cells. Blood 2004; 103: 2332-6.
30. Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res 2008; 6: 190-7.
31. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007; 67: 1030-7.
32. Simeone DM. Pancreatic cancer stem cells: implications for the treatment of pancreatic cancer. Clin Cancer Res 2008; 14: 5646-8.
33. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007; 104: 973-8.
34. Kruger JA, Kaplan CD, Luo Y, Zhou H, Markowitz D, Xiang R, et al. Characterization of stem cell-like cancer cells in immune-competent mice. Blood 2006; 108: 3906-12.
35. Deeley RG, Westlake C, Cole SPC. Transmembrane transport of Endo-and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev 2006; 86: 849-99.
36. Roy S, Srivastava R, Shankar S. Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J Mol Signal 2010; 5: 10.
37. Chen AM, Zhang M, Wei D, Stueber D, Taratula O, Minko T, et al. Co-delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrugresistant cancer cells. Small 2009; 5: 2673-7.
38. Guo G, Qiu X, Wang S, Chen Y, Rothman PB, Wang Z, et al. Oncogenic E17K mutation in the pleckstrin homology domain of AKT1 promotes v-Abl-mediated pre-B-cell transformation and survival of Pim-deficient cells. Oncogene 2010; 29: 3845-53.
39. Baud V, Karin M. Is NF-[kappa]B a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 2009; 8: 33-40.
40. Burger JA, Peled A. CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers. Leukemia 2008; 23: 43-52.
41. Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 2007; 1: 389-402.
42. Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res 2010; 70: 709-18.
43. Murphy M, Stordal B. Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review. Drug Resistance Updates 2011; 14: 177-90.
44. Gutierrez A, Sanda T, Grebliunaite R, Carracedo A, Salmena L, Ahn Y, et al. High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia. Blood 2009; 114: 647-50.
45. Chen JL, Limnander A, Rothman PB. Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene. Blood 2008; 111: 1677-85.
46. Pradhan A, Lambert QT, Reuther GW. Transformation of hematopoietic cells and activation of JAK2-V617F by IL-27R, a component of a heterodimeric type I cytokine receptor. Proc Natl Acad Sci USA 2007; 104: 18502-7.
47. Qiu X, Guo G, Chen K, Kashiwada M, Druker BJ, Rothman PB, et al. A requirement for SOCS-1 and SOCS-3 phosphorylation in Bcr-Ablinduced tumorigenesis. Neoplasia 2012; 14: 547-58.
48. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140: 883-99.
49. Chaturvedi MM, Sung B, Yadav VR, Kannappan R, Aggarwal BB. NF-[kappa]B addiction and its role in cancer: one size does not fit all. Oncogene 2011; 30: 1615-30.
50. Dontu G, Jackson K, McNicholas E, Kawamura M, Abdallah W, Wicha M. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res 2004; 6: R605-R615.
51. Merchant AA, Matsui W. Targeting Hedgehog-a cancer stem cell pathway. Clin Cancer Res 2010; 16: 3130-40.
52. Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, et al. Cutaneous cancer stem cell maintenance is dependent on [bgr]-catenin signalling. Nature 2008; 452: 650-3.
53. Zeng YA, Nusse R. Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture. Cell Stem Cell 2010; 6: 568-77.
54. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005; 434: 843-50.
55. Cho K, Wang X, Nie S, Chen Z, Shin DM. Therapeutic nanoparticles for drug Delivery in cancer. Clin Cancer Res 2008; 14: 1310-6.
56. LaBarge MA. The difficulty of targeting cancer stem cell niches. Clin Cancer Res 2010; 16: 3121-9.
57. Lacerda L, Pusztai L, Woodward WA. The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches. Drug Resist Updat 2010; 13: 99-108.
58. Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S, et al. Targeting miRNAs involved in cancer stem cell and EMT regulation: an emerging concept in overcoming drug resistance. Drug Resist Updat 2010; 13: 109-18.
59. Liu J, Kopeckova P, Buhler P, Wolf P, Pan H, Bauer H, et al. Biorecognition and subcellular trafficking of HPMA copolymer-anti-PSMA antibody conjugates by prostate cancer cells. Mol Pharm 2009; 6: 959-70.
60. Curiel TJ. Immunotherapy: a useful strategy to help combat multidrug resistance. Drug Resistance Updates 2012; 15: 106-13.
61. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 2006; 12: 1167-74.
62. Jin L, Lee EM, Ramshaw HS, Busfield SJ, Peoppl AG, Wilkinson L, et al. Monoclonal antibody-mediated targeting of CD123, IL-3 receptor ? chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell 2009; 5: 31-42.
63. Kikushige Y, Shima T, Takayanagi S, Urata S, Miyamoto T, Iwasaki H, et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell 2010; 7: 708-17.
64. Chao MP, Alizadeh AA, Tang C, Jan M, Weissman-Tsukamoto R, Zhao F, et al. Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia. Cancer Res 2011; 71: 1374-84.
65. Alkilany AM, Thompson LB, Boulos SP, Sisco PN, Murphy CJ. Gold nanorods: Their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions. Adv Drug Deliv Rev 2012; 64: 190-9.
66. Gundlach CW 4th, Caivano A, da Graca Cabreira-Hansen M, Gahremanpour A, Brown WS, Zheng Y, et al. Synthesis and evaluation of an anti-MLC1×anti- CD90 bispecific antibody for targeting and retaining bone-marrow-derived multipotent stromal cells in infarcted myocardium. Bioconjug Chem 2011; 22: 1706-14.
67. Lin EH, Hassan M, Li Y, Zhao H, Nooka A, Sorenson E, et al. Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence. Cancer 2007; 110: 534-42.
68. Mehra N, Penning M, Maas J, Beerepoot LV, van Daal N, van Gils CH, et al. Progenitor marker CD133 mRNA Is elevated in peripheral blood of cancer patients with bone metastases. Clin Cancer Res 2006; 12: 4859-66.
69. Wang CH, Chiou SH, Chou CP, Chen YC, Huang YJ, Peng CA. Photothermolysis of glioblastoma stem-like cells targeted by carbon nanotubes conjugated with CD133 monoclonal antibody. Nanomedicine 2011; 7: 69-79.
70. Paola B, Barbara O, Lorenzo F, Daniel L, Giovanni B, Giuliana P. CD133 is essential for glioblastoma stem cell maintenance. STEM CELLS 2013: n/a-n/a.
71. Broxterman HJ, Gotink KJ, Verheul HMW. Understanding the causes of multidrug resistance in cancer: a comparison of doxorubicin and sunitinib. Drug Resist Updat 2009; 12: 114-26.
72. Shapira A, Livney YD, Broxterman HJ, Assaraf YG. Nanomedicine for targeted cancer therapy: Towards the overcoming of drug resistance. Drug Resist Updat 2011; 14: 150-63.
73. Patil Y, Sadhukha T, Ma L, Panyam J. Nanoparticle-mediated simultaneous and targeted delivery of paclitaxel and tariquidar overcomes tumor drug resistance. J Control Release 2009; 136: 21-9.
74. Ritchie TK, Kwon H, Atkins WM. Conformational analysis of Human ATP-binding cassette transporter ABCB1 in lipid nanodiscs and Inhibition by the antibodies MRK16 and UIC2. J Biol Chem 2011; 286: 39489-96.
75. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 1981; 41: 1967-72.
76. Khdair A, Di C, Patil Y, Ma L, Dou QP, Shekhar MPV, et al. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance. J Control Release 2010; 141: 137-44.
77. Saeki T, Nomizu T, Toi M, Ito Y, Noguchi S, Kobayashi T, et al. Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin, and fluorouracil for patients with advanced or recurrent breast cancer. J Clin Oncol 2007; 25: 411-7.
78. Minderman H, O'Loughlin KL, Pendyala L, Baer MR. VX-710 (Biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Clin Cancer Res 2004; 10: 1826-34.
79. Sims-Mourtada J, Izzo JG, Ajani J, Chao KSC. Sonic hedgehog promotes multiple drug resistance by regulation of drug transport. Oncogene 2007; 26: 5674-9.
80. Fischer M, Yen WC, Kapoun AM, Wang M, O'Young G, Lewicki J, et al. Anti-DLL4 inhibits growth and reduces tumor-initiating cell frequency in colorectal tumors with oncogenic KRAS mutations. Cancer Res 2011; 71: 1520-5.
81. Li K, Li Y, Wu W, Gordon WR, Chang DW, Lu M, et al. Modulation of notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3. J Biol Chem 2008; 283: 8046-54.
82. McGowan PM, Simedrea C, Ribot EJ, Foster PJ, Palmieri D, Steeg PS, et al. Notch1 inhibition alters the CD44hi/CD24lo population and reduces the formation of brain metastases from breast cancer. Mol Cancer Res 2011; 9: 834-44.
83. Vermeulen L, De Sousa E Melo F, van der Heijden M, Cameron K, de Jong JH, Borovski T, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 2010; 12: 468-76.
84. Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan CW, et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol 2009; 5: 100-7.
85. Fujii N, You L, Xu Z, Uematsu K, Shan J, He B, et al. An antagonist of dishevelled protein-protein interaction suppresses ?-catenindependent tumor cell frowth. Cancer Res 2007; 67: 573-9.
86. He B, Reguart N, You L, Mazieres J, Xu Z, Lee AY, et al. Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations. Oncogene 2005; 24: 3054-8.
87. Feldmann G, Fendrich V, McGovern K, Bedja D, Bisht S, Alvarez H, et al. An orally bioavailable small-molecule inhibitor of hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Mol Cancer Ther 2008; 7: 2725-35.
88. Ramaswamy B, Lu Y, Teng KY, Nuovo G, Li X, Shapiro CL, et al. Hedgehog signaling Is a novel therapeutic target in tamoxifenresistant breast cancer abarrantly activated by PI3K/AKT pathway. Cancer Res 2012; 72: 5048-59.
89. Feldmann G, Habbe N, Dhara S, Bisht S, Alvarez H, Fendrich V, et al. Hedgehog inhibition prolongs survival in a genetically engineered mouse model of pancreatic cancer. Gut 2008; 57: 1420-30.
90. Karhadkar SS, Steven Bova G, Abdallah N, Dhara S, Gardner D, Maitra A, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 2004; 431: 707-12.
91. Bar EE, Chaudhry A, Lin A, Fan X, Schreck K, Matsui W, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stemlike cancer cells in glioblastoma. stem cells 2007; 25: 2524-33.
92. Feldmann G, Dhara S, Fendrich V, Bedja D, Beaty R, Mullendore M, et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 2007; 67: 2187-96.
93. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 2007; 17: 165-72.
94. Fan L, Li F, Zhang H, Wang Y, Cheng C, Li X, et al. Co-delivery of PDTC and doxorubicin by multifunctional micellar nanoparticles to achieve active targeted drug delivery and overcome multidrug resistance. Biomaterials 2010; 31: 5634-42.
95. Ganta S, Amiji M. Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Mol Pharm 2009; 6: 928-39.
96. Bentires-Alj M, Barbu V, Fillet M, Chariot A, Relic B, Jacobs N, et al. NF-[kappa]B transcription factor induces drug resistance through MDR1 expression in cancer cells. Oncogene 2003; 22: 90-7.
97. Devalapally H, Duan Z, Seiden MV, Amiji MM. Modulation of drug resistance in ovarian adenocarcinoma by enhancing intracellular ceramide using tamoxifen-loaded biodegradable polymeric Nanoparticles. Clin Cancer Res 2008; 14: 3193-203.
98. Konopleva M, Tabe Y, Zeng Z, Andreeff M. Therapeutic targeting of microenvironmental interactions in leukemia: mechanisms and approaches. Drug Resist Updat 2009; 12: 103-13.
99. Burkhardt JK, Hofstetter CP, Santillan A, Shin BJ, Foley CP, Ballon DJ, et al. Orthotopic glioblastoma stem-like cell xenograft model in mice to evaluate intra-arterial delivery of bevacizumab: from bedside to bench. J Clin Neurosci 2012; 19: 1568-72.
100. Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, et al. A perivascular niche for brain tumor stem cells. Cancer Cell 2007; 11: 69-82.
101. Folkins C, Man S, Xu P, Shaked Y, Hicklin DJ, Kerbel RS. Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res 2007; 67: 3560-4.
102. Lee ES, Gao Z, Kim D, Park K, Kwon IC, Bae YH. Super pH-sensitive multifunctional polymeric micelle for tumor pHe specific TAT exposure and multidrug resistance. J Control Release 2008; 129: 228-36.