International Journal of Radiation Oncology * Biology * Physics
Volume 74, Issue 5 , Pages 1580-1591 , 1 August 2009

Radiation Therapy Oncology Group Translational Research Program Stem Cell Symposium: Incorporating Stem Cell Hypotheses into Clinical Trials

  • Wendy A. Woodward, M.D., Ph.D.

      Affiliations

    • The University of Texas M. D. Anderson Cancer Center, Houston, TX
    • Corresponding Author InformationReprint requests to: Wendy A. Woodward, M.D., Ph.D., The University of Texas M. D. Anderson Cancer Center, Department of Radiation Oncology, 1515 Holcombe Blvd, Unit 1202, Houston, TX 77030. Tel: (713) 563-2300; Fax: (713) 563-6940
    • ,
  • Robert G. Bristow, M.D., Ph.D., FRCPC

      Affiliations

    • The Princess Margaret Hospital (University Health Network), Toronto, Ontario
    • ,
  • Michael F. Clarke, Ph.D.

      Affiliations

    • The University of Texas M. D. Anderson Cancer Center, Houston, TX
    • Stanford University, Palo Alto, CA
    • ,
  • Robert P. Coppes, Ph.D.

      Affiliations

    • University Medical Center Groningen, The Netherlands
    • ,
  • Massimo Cristofanilli, Ph.D.

      Affiliations

    • The University of Texas M. D. Anderson Cancer Center, Houston, TX
    • ,
  • Dan G. Duda, D.M.D., Ph.D.

      Affiliations

    • Massachusetts General Hospital, Harvard Medical School, Boston, MA
    • ,
  • John R. Fike, Ph.D.

      Affiliations

    • The University of California, San Francisco, CA
    • ,
  • Dolores Hambardzumyan, Ph.D.

      Affiliations

    • The Princess Margaret Hospital (University Health Network), Toronto, Ontario
    • Memorial Sloan-Kettering Cancer Center, New York, NY
    • ,
  • Richard P. Hill, Ph.D.

      Affiliations

    • The Princess Margaret Hospital (University Health Network), Toronto, Ontario
    • ,
  • Craig T. Jordan, Ph.D.

      Affiliations

    • The University of Rochester Medical Center, Rochester, NY
    • ,
  • Luka Milas, M.D., Ph.D.

      Affiliations

    • The University of Texas M. D. Anderson Cancer Center, Houston, TX
    • ,
  • Frank Pajonk, M.D.

      Affiliations

    • The University of California, Los Angeles, Los Angeles, CA
    • ,
  • Walter J. Curran, M.D.

      Affiliations

    • Thomas Jefferson University, Philadelphia, PA
    • ,
  • Adam P. Dicker, M.D., Ph.D.

      Affiliations

    • Thomas Jefferson University, Philadelphia, PA
    • ,
  • Yuhchyau Chen, PhD., M.D.

      Affiliations

    • The University of Rochester Medical Center, Rochester, NY

Received 25 February 2009 ,Accepted 3 March 2009.

References 

  1. Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer. 2003;3:895–902
  2. Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–111
  3. Woodward WA, Sulman EP. Cancer stem cells: markers or biomarkers?. Cancer Metastasis Rev. 2008;27:459–470
  4. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–3988
  5. Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006;355:1253–1261
  6. O'Brien CA, Pollett A, Gallinger S, et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–110
  7. Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–5828
  8. Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–760
  9. Guenechea G, Gan OI, Dorrell C, et al. Distinct classes of human stem cells that differ in proliferative and self-renewal potential. Nat.Immunol. 2001;2:75–82
  10. Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol. 2004;5:738–743
  11. Krivtsov AV, Feng Z, Lemieux M, et al. Global Increase in H3K79 dimethylation in murine and human MLL-AF4 lymphoblastic leukemias. Blood (ASH Annual Meeting Abstracts). 2007;110:344
  12. Phillips TM, McBride WH, Pajonk F. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst. 2006;98:1777–1785
  13. Woodward WA, Chen MS, Behbod F, et al. WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci U S A. 2007;104:618–623
  14. Wang JC. Evaluating therapeutic efficacy against cancer stem cells: New challenges posed by a new paradigm. Cell Stem Cell. 2007;1:497–501
  15. Calabrese C, Poppleton H, Kocak M, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11:69–82
  16. Hambardzumyan D, Becher OJ, Rosenblum MK, et al. PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes Dev. 2008;22:436–448
  17. Dontu G, Jackson KW, McNicholas E, et al. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res. 2004;6:R605–R615
  18. Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: Randomised, double-blind, placebo-controlled trial. Lancet. 2003;362:1255–1260
  19. Vlashi E, Kim K, Lagadec C, et al. In vivo imaging, tracking, and targeting of cancer stem cells. J Natl Cancer Inst. 2009;101:350–359
  20. Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer. 2008;8:545–554
  21. Taghian A, DuBois W, Budach W, et al. In vivo radiation sensitivity of glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 1995;32:99–104
  22. Mimeault M, Hauke R, Batra SK. Stem cells: A revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies. Clin Pharmacol Ther. 2007;82:252–264
  23. Bearzi C, Rota M, Hosoda T, et al. Human cardiac stem cells. Proc Natl Acad Sci U S A. 2007;104:14068–14073
  24. Bussolati B, Bruno S, Grange C, et al. Isolation of renal progenitor cells from adult human kidney. Am J Pathol. 2005;166:545–555
  25. Meissner KK, Kirkham DL, Doering LC. Transplants of neurosphere cell suspensions from aged mice are functional in the mouse model of Parkinson's. Brain Res. 2005;1057:105–112
  26. Serrano-Mollar A, Nacher M, Gay-Jordi G, et al. Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis. Am J Respir Crit Care Med. 2007;176:1261–1268
  27. Shackleton M, Vaillant F, Simpson KJ, et al. Generation of a functional mammary gland from a single stem cell. Nature. 2006;439:84–88
  28. Lombaert IM, Brunsting JF, Wierenga PK, et al. Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS ONE. 2008;3:e2063
  29. Eckfeldt CE, Mendenhall EM, Verfaillie CM. The molecular repertoire of the 'almighty' stem cell. Nat Rev Mol Cell Biol. 2005;6:726–737
  30. Lombaert IM, Brunsting JF, Wierenga PK, et al. Cytokine treatment improves parenchymal and vascular damage of salivary glands after irradiation. Clin Cancer Res. 2008;14:7741–7750
  31. Lombaert IM, Wierenga PK, Kok T, et al. Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands. Clin Cancer Res. 2006;12:1804–1812
  32. Lombaert IM, Brunsting JF, Wierenga PK, et al. Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool. Stem Cells. 2008;26:2595–2601
  33. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–967
  34. Yoder MC, Mead LE, Prater D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007;109:1801–1809
  35. Ahn GO, Brown JM. Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: Role of bone marrow-derived myelomonocytic cells. Cancer Cell. 2008;13:193–205
  36. Lyden D, Hattori K, Dias S, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med. 2001;7:1194–1201
  37. Jain RK, Duda DG. Role of bone marrow-derived cells in tumor angiogenesis and treatment. Cancer Cell. 2003;3:515–516
  38. Jain RK, di Tomaso E, Duda DG, et al. Angiogenesis in brain tumours. Nat Rev Neurosci. 2007;8:610–622
  39. Duda DG, Cohen KS, Kozin SV, et al. Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors. Blood. 2006;107:2774–2776
  40. Garcia-Barros M, Paris F, Cordon-Cardo C, et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003;300:1155–1159
  41. De Palma M, Venneri MA, Roca C, et al. Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat Med. 2003;9:789–795
  42. Au P, Daheron LM, Duda DG, et al. Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels. Blood. 2008;111:1302–1305
  43. Duda DG, Cohen KS, di Tomaso E, et al. Differential CD146 expression on circulating versus tissue endothelial cells in rectal cancer patients: Implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy. J Clin Oncol. 2006;24:1449–1453
  44. Duda DG, Cohen KS, Scadden DT, et al. A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood. Nat Protoc. 2007;2:805–810
  45. Batchelor TT, Sorensen AG, di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007;11:83–95
  46. Willett CG, Duda DG, di Tomaso E, et al. Efficacy, safety and biomarkers of neoadjuvant bevacizumab, radiation therapy and 5-Fluorouracil in rectal cancer: A multidisciplinary phase II Study. J Clin Oncol. In press.
  47. Zhu AX, Sahani DV, Duda DG, et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: A Phase II study. J Clin Oncol. In press.
  48. Mizumatsu S, Monje ML, Morhardt DR, et al. Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res. 2003;63:4021–4027
  49. Kee N, Teixeira CM, Wang AH, et al. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci. 2007;10:355–362
  50. Raber J, Rola R, LeFevour A, et al. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat Res. 2004;162:39–47
  51. Rola R, Mizumatsu S, Otsuka S, et al. Alterations in hippocampal neurogenesis following traumatic brain injury in mice. Exp Neurol. 2006;202:189–199
  52. Snyder JS, Hong NS, McDonald RJ, et al. A role for adult neurogenesis in spatial long-term memory. Neuroscience. 2005;130:843–852
  53. Monje ML, Mizumatsu S, Fike JR, et al. Irradiation induces neural precursor-cell dysfunction. Nat Med. 2002;8:955–962
  54. Fike JR, Rola R, Limoli CL. Radiation response of neural precursor cells. Neurosurg Clin N Am. 2007;18:115–127x
  55. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science. 2003;302:1760–1765
  56. Limoli CL, Giedzinski E, Rola R, et al. Radiation response of neural precursor cells: Linking cellular sensitivity to cell cycle checkpoints, apoptosis and oxidative stress. Radiat Res. 2004;161:17–27
  57. Limoli CL, Rola R, Giedzinski E, et al. Cell-density-dependent regulation of neural precursor cell function. Proc Natl Acad Sci U S A. 2004;101:16052–16057
  58. Balic M, Lin H, Young L, et al. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 2006;12:5615–5621
  59. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–791
  60. Li C, Heidt D, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–1037
  61. Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104:10158–10163
  62. Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A. 2007;104:973–978

 Conflict of interest: none.

 Supported by The RTOG grants # U10CA21661 and #U24 CA114734.

PII: S0360-3016(09)00507-0

doi: 10.1016/j.ijrobp.2009.03.047

International Journal of Radiation Oncology * Biology * Physics
Volume 74, Issue 5 , Pages 1580-1591 , 1 August 2009

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