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Cancer stem cell definitions and terminology: the devil is in the details

Abstract

The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and functional, properties has added to the confusion and has fuelled new ideas and controversies. Participants in The Year 2011 Working Conference on CSCs met to review these issues and to propose a conceptual and practical framework for CSC terminology. More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is also recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients.

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Figure 1: Models of cancer stem cell evolution: perturbation of the normal differentiation hierarchy.
Figure 2: Proposed model of cancer stem cell evolution.
Figure 3: Effects of therapies.

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References

  1. Reya, T., Morrison, S. J., Clarke, M. F. & Weissman, I. L. Stem cells, cancer, and cancer stem cells. Nature 414, 105–111 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Clarke, M. F. et al. Cancer stem cells-perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 66, 9339–9344 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Nguyen, L. V., Vanner, R., Dirks, P. & Eaves, C. J. Cancer stem cells: an evolving concept. Nature Rev. Cancer 12, 133–143 (2012).

    CAS  PubMed  Google Scholar 

  4. Schulenburg, A. et al. Neoplastic stem cells: current concepts and clinical perspectives. Crit. Rev. Oncol. Hematol. 76, 2512–2520 (2010).

    Google Scholar 

  5. Nowell, P. C. The clonal evolution of tumor cell populations. Science 194, 23–81 (1976).

    CAS  PubMed  Google Scholar 

  6. Baylin, S. B. & Jones, P. A. A decade of exploring the cancer epigenome - biological and translational implications. Nature Rev. Cancer 11, 726–734 (2011).

    CAS  Google Scholar 

  7. Greaves, M. & Maley, C. C. Clonal evolution in cancer. Nature 481, 306–313 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Stratton, M. R. Exploring the genomes of cancer cells: progress and promise. Science 331, 1553–1558 (2011).

    CAS  PubMed  Google Scholar 

  9. Magee, J. A., Piskounova, E. & Morrison, S. J. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 21, 283–296 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Singh, A. & Settleman, J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29, 4741–4751 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Konopleva, M. Y. & Jordan, C. T. Leukemia stem cells and microenvironment: biology and therapeutic targeting. J. Clin. Oncol. 29, 591–599 (2011).

    PubMed  PubMed Central  Google Scholar 

  12. Visvader, J. E. & Lindeman, G. J. Cancer stem cells: current status and evolving complexities. Cell Stem Cell 10, 717–728 (2012).

    CAS  PubMed  Google Scholar 

  13. Gillies, R. J., Verduzco, D. & Gatenby, R. A. Evolutionary dynamics of carcinogenesis and why targeted therapy does not work. Nature Rev. Cancer 12, 487–493 (2012).

    CAS  Google Scholar 

  14. Singh, S. K. et al. Identification of human brain tumour initiating cells. Nature 432, 396–401 (2004).

    CAS  PubMed  Google Scholar 

  15. Ponti, D. et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65, 5506–5511 (2005).

    CAS  PubMed  Google Scholar 

  16. Ricci-Vitiani, L. et al. Identification and expansion of human colon-cancer-initiating cells. Nature 445, 111–115 (2007).

    CAS  PubMed  Google Scholar 

  17. Eramo, A. et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 15, 504–514 (2008).

    CAS  PubMed  Google Scholar 

  18. Han, M. E. et al. Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research. Cell. Mol. Life Sci. 68, 3589–3605 (2011).

    CAS  PubMed  Google Scholar 

  19. Copley, M. R. Beer, P. A. & Eaves, C. J. Hematopoietic stem cell heterogeneity takes center stage. Cell Stem Cell 10, 690–697 (2012).

    CAS  PubMed  Google Scholar 

  20. Bixby, S., Kruger, G. M., Mosher, J. T., Joseph, N. M. & Morrison, S. J. Cell-intrinsic differences between stem cells from different regions of the peripheral nervous system regulate the generation of neural diversity. Neuron 35, 643–656 (2002).

    CAS  PubMed  Google Scholar 

  21. Van Keymeulen, A. & Blanpain, C. Tracing epithelial stem cells during development, homeostasis, and repair. J. Cell Biol. 197, 575–584 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Graf, T. & Enver, T. Forcing cells to change lineages. Nature 462, 587–594 (2009).

    CAS  PubMed  Google Scholar 

  23. Doulatov, S., Notta, F., Laurenti, E. & Dick, J. E. Hematopoiesis: a human perspective. Cell Stem Cell 10, 120–136 (2012).

    CAS  PubMed  Google Scholar 

  24. Smalley, M. J. et al. Isolation of mouse mammary epithelial subpopulations: a comparison of leading methods. J. Mammary Gland Biol. Neoplasia 17, 91–97 (2012).

    PubMed  Google Scholar 

  25. Wagers, A. J. & Conboy, I. M. Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell 122, 659–667 (2005).

    CAS  PubMed  Google Scholar 

  26. Stephens, P. J. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144, 27–40 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Gerlinger, M. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883–892 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Sutherland, H. J., Lansdorp, P. M., Henkelman, D. H., Eaves, A. C. & Eaves, C. J. Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. Proc. Natl Acad. Sci. USA 87, 3584–3358 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Uchida, N. et al. Direct isolation of human central nervous system stem cells. Proc. Natl Acad. Sci. USA 97, 14270–14275 (2000).

    Google Scholar 

  30. Dontu, G. et al. In vitro propagation and transcriptional profiling of human mammary/stem progenitor cells. Genes Dev. 17, 1253–1270 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kamel-Reid, S. et al. A model of human acute lymphoblastic leukemia in immune-deficient SCID mice. Science 246, 1597–1600 (1989).

    CAS  PubMed  Google Scholar 

  32. Lapidot, T. et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367, 645–648 (1994).

    CAS  PubMed  Google Scholar 

  33. Sirard, C. et al. Normal and leukemic SCID-repopulating cells (SRC) coexist in the bone marrow and peripheral blood from CML patients in chronic phase, whereas leukemic SRC are detected in blast crisis. Blood 87, 1539–1548 (1996).

    CAS  PubMed  Google Scholar 

  34. Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. & Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA 100, 3983–3988 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. O'Brien, C. A., Pollett, A., Gallinger, S. & Dick, J. E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106–110 (2007).

    CAS  PubMed  Google Scholar 

  36. Stewart, J. M. et al. Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells. Proc. Natl Acad. Sci. USA 108, 6468–6473 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Prince, M. E. 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 104, 973–978 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Taussig, D. C. et al. Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells. Blood 112, 568–575 (2008).

    CAS  PubMed  Google Scholar 

  39. Taussig, D. C. et al. Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34- fraction. Blood 115, 1976–1984 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Goardon, N. et al. Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell 19, 138–152 (2011).

    CAS  PubMed  Google Scholar 

  41. Weinberg, O. K. & Arber, D. A. Mixed-phenotype acute leukemia: historical overview and a new definition. Leukemia 24, 1844–1851 (2010).

    CAS  PubMed  Google Scholar 

  42. Kong, Y. et al. CD34+CD38+CD19+ as well as CD34+CD38-CD19+ cells are leukemia-initiating cells with self-renewal capacity in human B-precursor ALL. Leukemia 22, 1207–1213 (2008).

    CAS  PubMed  Google Scholar 

  43. Dirks, P. B. Brain tumor stem cells: the cancer stem cell hypothesis writ large. Mol. Oncol. 4, 420–430 (2010).

    PubMed  PubMed Central  Google Scholar 

  44. Shmelkov, S. V. et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumours. J. Clin. Invest. 118, 2111–2120 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Quintana, E. et al. Phenotypic heterogeneity among tumourigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer Cell 18, 510–523 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Quintana, E. et al. Efficient tumour formation by single human melanoma cells. Nature 456, 593–598 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Gupta, P. B., Chaffer, C. L. & Weinberg, R. A. Cancer stem cells: mirage or reality? Nature Med. 15, 1010–1012 (2009).

    CAS  PubMed  Google Scholar 

  48. Gupta, P. B. et al. Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell 146, 633–644 (2011).

    CAS  PubMed  Google Scholar 

  49. Roesch, A. et al. A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumour growth. Cell 141, 583–594 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Chaffer, C. L. et al. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc. Natl Acad. Sci. USA 108, 7950–7955 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Baylin, S. B. & Jones, P. A. A decade of exploring the cancer epigenome – biological and translational implications. Nature Rev. Cancer 11, 726–734 (2011).

    CAS  Google Scholar 

  52. Okita, K. & Yamanaka, S. Induced pluripotent stem cells: opportunities and challenges. Philosoph. Trans. R. Soc. B. Biol. Sci. 366, 2198–2207 (2011).

    CAS  Google Scholar 

  53. Akkina, R. et al. Humanized Rag1−/− γc−/− mice support multilineage hematopoiesis and are susceptible to HIV-1 infection via systemic and vaginal routes. PLoS ONE 6, e20169 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Strowig, T. et al. Transgenic expression of human signal regulatory protein α in Rag2−/−γc−/− mice improves engraftment of human hematopoietic cells in humanized mice. Proc. Natl Acad. Sci. USA 108, 13218–13223 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Wunderlich, M. et al. AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia 24, 1785–1788 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Takagi, S. et al. Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation. Blood 119, 2768–2777 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Lan, P., Tonomura, N., Shimizu, A., Wang, S. & Yang, Y. G. Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation. Blood 108, 487–492 (2006).

    CAS  PubMed  Google Scholar 

  58. Petzer, A. L. et al. Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia. Blood 88, 2162–2171 (1996).

    CAS  PubMed  Google Scholar 

  59. Blair, A., Hogge, D. E., Ailles, L. E., Lansdorp, P. M. & Sutherland, H. J. Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood 89, 3104–3112 (1997).

    CAS  PubMed  Google Scholar 

  60. Garnett, M. J. et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 483, 570–575 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Chen, J. et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488, 522–526 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Schepers, A. G. et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337, 730–735 (2012).

    CAS  PubMed  Google Scholar 

  63. Driessens, G., Beck, B., Caauwe, A., Simons, B. D. & Blanpain, C. Defining the mode of tumour growth by clonal analysis. Nature 488, 527–530 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Domanska, U. M. et al. A review on CXCR4/CXCL12 axis in oncology: no place to hide. Eur. J. Cancer 8 Jun 2012 [epub ahead of print].

  65. Damon, L. E. & Damon, L. E. Mobilization of hematopoietic stem cells into the peripheral blood. Exp. Rev. Hematol. 2, 717–733 (2009).

    CAS  Google Scholar 

  66. Kessans, M. R., Gatesman, M. L. & Kockler, D. R. Plerixafor: a peripheral blood stem cell mobilizer. Pharmacotherapy 30, 485–492 (2010).

    CAS  PubMed  Google Scholar 

  67. Burger, J. A. & Peled, A. CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers. Leukemia 23, 43–52 (2009).

    CAS  PubMed  Google Scholar 

  68. Jin, L., Hope, K. J., Zhai, Q., Smadja-Joffe, F. & Dick, J. E. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nature Med. 12, 1167–1174 (2006).

    PubMed  Google Scholar 

  69. Florian, S. et al. Detection of molecular targets on the surface of CD34+/CD38- stem cells in various myeloid malignancies. Leuk. Lymphoma 47, 207–222 (2006).

    CAS  PubMed  Google Scholar 

  70. Hosen, N. et al. CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc. Natl Acad. Sci. USA 104, 11008–11013 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Van Rhenen, A. et al. The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood 110, 2659–2666 (2007).

    CAS  PubMed  Google Scholar 

  72. Jin, L. et al. Monoclonal antibody-mediated targeting of CD123, IL-3 receptor α chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell 5, 31–42 (2009).

    CAS  PubMed  Google Scholar 

  73. Järås, M. et al. Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. Proc. Natl Acad. Sci. USA 107, 16280–16285 (2010).

    PubMed  PubMed Central  Google Scholar 

  74. Kemper, K., Grandela, C. & Medema, J. P. Molecular identification and targeting of colorectal cancer stem cells. Oncotarget 1, 387–395 (2010).

    PubMed  PubMed Central  Google Scholar 

  75. Lorico, A. & Rappa, G. Phenotypic heterogeneity of breast cancer stem cells. J. Oncol. 2011, 135039 (2011).

    PubMed  PubMed Central  Google Scholar 

  76. Korkaya, H. & Wicha, M. S. Selective targeting of cancer stem cells: a new concept in cancer therapeutics. BioDrugs 21, 299–310 (2007).

    CAS  PubMed  Google Scholar 

  77. Valent, P. Emerging stem cell concepts for imatinib-resistant chronic myeloid leukaemia: implications for the biology, management, and therapy of the disease. Br. J. Haematol. 142, 361–378 (2008).

    CAS  PubMed  Google Scholar 

  78. Tu, L. C., Foltz, G., Lin, E., Hood, L. & Tian, Q. Targeting stem cells-clinical implications for cancer therapy. Curr. Stem Cell Res. Ther. 4, 147–153 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Gupta, P. B. et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138, 645–659 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Curtin, J. C. & Lorenzi, M. V. Drug discovery approaches to target Wnt signaling in cancer stem cells. Oncotarget 1, 563–577 (2010).

    PubMed  PubMed Central  Google Scholar 

  81. Pannuti, A. et al. Targeting Notch to target cancer stem cells. Clin. Cancer Res. 16, 3141–3152 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Martelli, A. M. et al. Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in cancer stem cells. Curr. Med. Chem. 18, 2715–2726 (2011).

    CAS  PubMed  Google Scholar 

  83. Allan, E. K., Holyoake, T. L., Craig, A. R. & Jørgensen, H. G. Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells. Leukemia 25, 985–994 (2011).

    CAS  PubMed  Google Scholar 

  84. Takebe, N., Harris, P. J., Warren, R. Q. & Ivy, S. P. Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nature Rev. Clin. Oncol. 8, 97–106 (2011).

    CAS  Google Scholar 

  85. de Sousa, E. M., Vermeulen, L., Richel, D. & Medema, J. P. Targeting Wnt signaling in colon cancer stem cells. Clin. Cancer Res. 17, 647–653 (2011).

    PubMed  Google Scholar 

  86. Wei, L. et al. Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial-mesenchymal transition and nuclear factor-κB. Breast Cancer Res. 13, R101 (2011).

    CAS  Google Scholar 

  87. Zuber, J. et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukemia. Nature 478, 524–528 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Dawson, M. A. et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia. Nature 478, 529–533 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Skrtic, M. et al. Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia. Cancer Cell 20, 674–688 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Sachlos, E. et al. Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells. Cell 149, 1284–1297 (2012).

    CAS  PubMed  Google Scholar 

  91. Valent, P. Targeting of leukemia-initiating cells to develop curative drug therapies: straightforward but nontrivial concept. Curr. Cancer Drug Targets 11, 56–71 (2011).

    CAS  PubMed  Google Scholar 

  92. Barnes, D. J. & Melo, J. V. Primitive, quiescent and difficult to kill: the role of non-proliferating stem cells in chronic myeloid leukemia. Cell Cycle 5, 2862–2866 (2006).

    CAS  PubMed  Google Scholar 

  93. Irish, J. M., Kotecha, N. & Nolan, G. P. Mapping normal and cancer cell signalling networks: towards single-cell proteomics. Nature Rev. Cancer 6, 146–155 (2006).

    CAS  Google Scholar 

  94. Ho, M. M., Hogge, D. E. & Ling, V. MDR1 and BCRP1 expression in leukemic progenitors correlates with chemotherapy response in acute myeloid Leukemia. Exp. Hematol. 36, 433–442 (2008).

    CAS  PubMed  Google Scholar 

  95. Rosen, D. B. et al. Distinct patterns of DNA damage response and apoptosis correlate with Jak/Stat and PI3 kinase response profiles in human myelogenous Leukemia. PLoS ONE 5, e12405 (2010).

    PubMed  PubMed Central  Google Scholar 

  96. de Jonge, H. J. et al. Gene expression profiling in the leukemic stem cell-enriched CD34+ fraction identifies target genes that predict prognosis in normal karyotype AML. Leukemia 25, 1825–1833 (2011).

    CAS  PubMed  Google Scholar 

  97. Eppert, K. et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nature Med. 17, 1086–1093 (2011).

    CAS  PubMed  Google Scholar 

  98. Melo, J. V. & Ross, D. M. Minimal residual disease and discontinuation of therapy in chronic myeloid leukemia: can we aim at a cure? Hematol. Am. Soc. Hematol. Educ. Program 2011, 136–142 (2011).

    Google Scholar 

  99. Liu, Y., Hernandez, A. M., Shibata, D. & Cortopassi, G. A. BCL2 translocation frequency rises with age in humans. Proc. Natl Acad. Sci. USA 91, 8910–8914 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Limpens, J. et al. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood 85, 2528–2536 (1995).

    CAS  PubMed  Google Scholar 

  101. Biernaux, C., Loos, M., Sels, A., Huez, G. & Stryckmans, P. Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals. Blood 86, 3118–3122 (1995).

    CAS  PubMed  Google Scholar 

  102. Cazzaniga, G. et al. Developmental origins and impact of BCR-ABL1 fusion and IKZF1 deletions in monozygotic twins with Ph+ acute lymphoblastic leukemia. Blood 118, 5559–5564 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Leary, R. J. et al. Development of personalized tumor biomarkers using massively parallel sequencing. Sci. Transl. Med. 2, 20ra14 (2010).

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The Year 2011 Working Conference on Cancer Stem Cells was supported by a Cancer Stem Cell Grant of the Medical University of Vienna, Austria. The authors would like to thank S. Sonnleitner and K. Krassel for their helpful technical support. H.E.J. was supported by the EU 6th FP to MSCNET (LSHC-CT-2006-037602). M.C. is supported by a Fellowship from the Scottish Funding Council (SCD/04) and J.V.M. by the NIHR Biomedical Research Centre Funding Scheme, UK.

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Classification of therapies according to their effects (PDF 427 kb)

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Overview of Mechanisms of CSC Resistance to Therapy and Strategies to Overcome Resistance (PDF 199 kb)

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Valent, P., Bonnet, D., De Maria, R. et al. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer 12, 767–775 (2012). https://doi.org/10.1038/nrc3368

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