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Strategies to Eliminate Cancer Stem Cells

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Cancer Stem Cells

Part of the book series: Springer Series on Biofilms ((SCHERING FOUND,volume 2006/5))

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Abstract

Therapeutic advances over the past three decades now allow most cancer patients to achieve major clinical responses. Although clinical responses can clearly decrease side effects and improve quality of life, most cancer patients still eventually relapse and die of their disease. Emerging data suggest that initial responses in cancer represent therapeutic effectiveness against the differentiated cancer cells making up the bulk of the tumor, while rare biologically distinct cancer stem cells resistant to the therapies are responsible for relapse. Better understanding the biology of cancer stem cells, and reexamining both our preclinical and clinical drug development paradigms to include the cancer stem cell concept, have the potential to revolutionize the treatment of many cancers.

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References

  • Al Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988

    Article  CAS  PubMed  Google Scholar 

  • Angstreich GR, Matsui W, Huff CA, Vala MS, Barber J, Hawkins AL, Griffin CA, Smith BD, Jones RJ (2005) Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors. Br J Haematol 130:373–381

    Article  CAS  PubMed  Google Scholar 

  • Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354:34–43

    Article  CAS  PubMed  Google Scholar 

  • Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 335:91–97

    Article  CAS  PubMed  Google Scholar 

  • Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD, McCoy J, Dakhil SR, Lanier KS, Chapman RA, Cromer JN, Salmon SE, Durie B, Crowley JC (2006) Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol 24:929–936

    Article  CAS  PubMed  Google Scholar 

  • Bedi A, Zehnbauer BA, Collector MI, Barber JP, Zicha MS, Sharkis SJ, Jones RJ (1993) BCR-ABL gene rearrangement and expression of primitive hematopoietic progenitors in chronic myeloid leukemia. Blood 81:2898–2902

    CAS  PubMed  Google Scholar 

  • Bonifazi F, de Vivo A, Rosti G, Guilhot F, Guilhot J, Trabacchi E, Hehlmann R, Hochhaus A, Shepherd PC, Steegmann JL, Kluin-Nelemans HC, Thaler J, Simonsson B, Louwagie A, Reiffers J, Mahon FX, Montefusco E, Alimena G, Hasford J, Richards S, Saglio G, Testoni N, Martinelli G, Tura S, Baccarani M (2001) Chronic myeloid leukemia and interferon-α: a study of complete cytogenetic responders. Blood 98:3074–3081

    Article  CAS  PubMed  Google Scholar 

  • Bunting KD (2002) ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells 20:11–20

    Article  CAS  PubMed  Google Scholar 

  • Burger H, van Tol H, Boersma AW, Brok M, Wiemer EA, Stoter G, Nooter K (2004) Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood 104:2940–2942

    Article  CAS  PubMed  Google Scholar 

  • Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ (2003) High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348:1875–1883

    Article  CAS  PubMed  Google Scholar 

  • Cortes J, O'Brien S, Kantarjian H (2004) Discontinuation of imatinib therapy after achieving a molecular response. Blood 104:2204–2205

    Article  CAS  PubMed  Google Scholar 

  • Dokal I, Vulliamy T (2003) Dyskeratosis congenita: its link to telomerase and aplastic anaemia. Blood Rev 17:217–225

    Article  PubMed  Google Scholar 

  • Durie BG, Jacobson J, Barlogie B, Crowley J (2004) Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in southwest oncology group chemotherapy trials. J Clin Oncol 22:1857–1863

    Article  PubMed  Google Scholar 

  • Fialkow PJ, Jacobson RJ, Papayannopoulou T (1977) Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am J Med 63:125–130

    Article  CAS  PubMed  Google Scholar 

  • Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, Sawyers CL (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293:876–880

    Article  CAS  PubMed  Google Scholar 

  • Graham SM, Jorgensen HG, Allan E, Pearson C, Alcorn MJ, Richmond L, Holyoake TL (2002) Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 99:319–325

    Article  CAS  PubMed  Google Scholar 

  • Greenberg RA, Chin L, Femino A, Lee KH, Gottlieb GJ, Singer RH, Greider CW, DePinho RA (1999) Short dysfunctional telomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse. Cell 97:515–525

    Article  CAS  PubMed  Google Scholar 

  • Hao LY, Armanios M, Strong MA, Karim B, Feldser DM, Huso D, Greider CW (2005) Short telomeres, even in the presence of telomerase, limit tissue renewal capacity. Cell 123:1121–1131

    Article  CAS  PubMed  Google Scholar 

  • Harrington L (2004) Does the reservoir for self-renewal stem from the ends? Oncogene 23:7283–7289

    Article  CAS  PubMed  Google Scholar 

  • Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA 100:15178–15183

    Article  CAS  PubMed  Google Scholar 

  • Hochhaus A, Kreil S, Corbin AS, La Rosee P, Muller MC, Lahaye T, Hanfstein B, Schoch C, Cross NC, Berger U, Gschaidmeier H, Druker BJ, Hehlmann R (2002) Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 16:2190–2196

    Article  CAS  PubMed  Google Scholar 

  • Holtz MS, Slovak ML, Zhang F, Sawyers CL, Forman SJ, Bhatia R (2002) Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation. Blood 99:3792–3800

    Article  CAS  PubMed  Google Scholar 

  • Horning SJ (1993) Natural history of and therapy for the indolent non-Hodgkin's lymphomas. Semin Oncol 20:75–88

    CAS  PubMed  Google Scholar 

  • Huff CA, Matsui W, Smith BD, Jones RJ (2006) The paradox of response and survival in cancer therapeutics. Blood 107:431–434

    Article  CAS  PubMed  Google Scholar 

  • Jiang G, Yang F, Li M, Weissbecker K, Price S, Kim KC, La Russa VF, Safah H, Ehrlich M (2003) Imatinib (ST1571) provides only limited selectivity for CML cells and treatment might be complicated by silent BCR-ABL genes. Cancer Biol Ther 2:103–108

    PubMed  Google Scholar 

  • Jones RJ, Matsui WH, Smith BD (2004) Cancer stem cells: are we missing the target? J Natl Cancer Inst 96:583–585

    Article  PubMed  Google Scholar 

  • Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121:823–835

    Article  CAS  PubMed  Google Scholar 

  • Levy V, Katsahian S, Fermand JP, Mary JY, Chevret S (2005) A meta-analysis on data from 575 patients with multiple myeloma randomly assigned to either high-dose therapy or conventional therapy. Medicine (Baltimore) 84:250–259

    Article  CAS  Google Scholar 

  • Mahon FX, Belloc F, Lagarde V, Chollet C, Moreau-Gaudry F, Reiffers J, Goldman JM, Melo JV (2003) MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 101:2368–2373

    Article  CAS  PubMed  Google Scholar 

  • Matsui W, Huff CA, Wang Q, Barber JP, Smith BD, Jones RJ (2004a) Multiple myeloma stem cells and plasma cells display distinct drug sensitivities. Blood 104:679a

    Google Scholar 

  • Matsui WH, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, Smith BD, Civin CI, Jones RJ (2004b) Characterization of clonogenic multiple myeloma cells. Blood 103:2332–2336

    Article  CAS  PubMed  Google Scholar 

  • Mauro MJ, Druker BJ, Kuyl J, Kurilik G, Maziarz RT (2003) Increasing levels of detectable leukemia in imatinib treated CML patients with previously undetectable or very low levels of BCR-ABL. Proc ASCO 22:569

    Google Scholar 

  • Mauro MJ, Druker BJ, Maziarz RT (2004) Divergent clinical outcome in two CML patients who discontinued imatinib therapy after achieving a molecular remission. Leuk Res 28(1):S71–S73

    Article  CAS  PubMed  Google Scholar 

  • Merante S, Orlandi E, Bernasconi P, Calatroni S, Boni M, Lazzarino M (2005) Outcome of four patients with chronic myeloid leukemia after imatinib mesylate discontinuation. Haematologica 90:979–981

    PubMed  Google Scholar 

  • Nilsson L, Astrand-Grundstrom I, Anderson K, Arvidsson I, Hokland P, Bryder D, Kjeldsen L, Johansson B, Hellstrom-Lindberg E, Hast R, Jacobsen SE (2002) Involvement and functional impairment of the CD34(+)CD38 − Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8. Blood 100:259–267

    CAS  PubMed  Google Scholar 

  • O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348:994–1004

    Article  PubMed  Google Scholar 

  • Raaijmakers MH, van Emst L, De Witte T, Mensink E, Raymakers RA (2002) Quantitative assessment of gene expression in highly purified hematopoietic cells using real-time reverse transcriptase polymerase chain reaction. Exp Hematol 30:481–487

    Article  CAS  PubMed  Google Scholar 

  • Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    Article  CAS  PubMed  Google Scholar 

  • Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348:2609–2617

    Article  CAS  PubMed  Google Scholar 

  • Roy L, Guilhot J, Krahnke T, Guerci-Bresler A, Druker BJ, Larson RA, O'Brien S, So C, Massimini G, Guilhot F (2006) Survival advantage from imatinib compared with the combination interferon-α plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials. Blood 108:1478–1484

    Article  CAS  PubMed  Google Scholar 

  • Rudolph KL, Millard M, Bosenberg MW, DePinho RA (2001) Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 28:155–159

    Article  CAS  PubMed  Google Scholar 

  • Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828

    CAS  PubMed  Google Scholar 

  • Treon SP, Pilarski LM, Belch AR, Kelliher A, Preffer FI, Shima Y, Mitsiades CS, Mitsiades NS, Szczepek AJ, Ellman L, Harmon D, Grossbard ML, Anderson KC (2002) CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications. J Immunother 25:72–81

    Article  PubMed  Google Scholar 

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Correspondence to R. J. Jones .

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O.D. Wiestler B. Haendler D. Mumberg

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© 2007 Springer-Verlag

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Jones, R.J. (2007). Strategies to Eliminate Cancer Stem Cells. In: Wiestler, O., Haendler, B., Mumberg, D. (eds) Cancer Stem Cells. Springer Series on Biofilms, vol 2006/5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/2789_2007_052

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  • DOI: https://doi.org/10.1007/2789_2007_052

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  • Print ISBN: 978-3-540-70852-0

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