Abstract
The cancer stem cell hypothesis is an attractive framework within which one may think about cancer initiation, recurrence, and metastasis, and methods to devise treatment strategies for cancers. Although all cancers do not appear to sustain themselves with cancer stem cells, but also through a dominant cell population, creating strategies for cancer treatment which include cancer stem cells as targets seems reasonable. In this perspective we discuss possible strategies for controlling the viability and tumorigenecity of cancer stem cells, and extend our discussion to strategies approaching the prevention of cancer.
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Adams, J. M., & Strasser, A. (2008). Is tumor growth sustained by rare cancer stem cells or dominant clones? Cancer Research, 68(11), 4018–4021.
Joseph, N. M., Mosher, J. T., Buchstaller, J., et al. (2008). The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Cancer Cells, 13(2), 129–140.
Zheng, H., Chang, L., Patel, N., et al. (2008). Induction of abnormal proliferation by nonmyelinating schwann cells triggers neurofibroma formation. Cancer Cells, 13(2), 117–128.
Clarke, M. F., & Fuller, M. (2006). Stem cells and cancer: two faces of eve. Cell, 124(6), 1111–1115.
Jordan, C. T., Guzman, M. L., & Noble, M. (2006). Cancer stem cells. New England Journal of Medicine, 355(12), 1253–1261.
Goldstein, N. S., Vicini, F. A., Hunter, S., Odish, E., Forbes, S., & Kestin, L. L. (2005). Molecular clonality relationships in initial carcinomas, ipsilateral breast failures, and distant metastases in patients treated with breast-conserving therapy: evidence suggesting that some distant metastases are derived from ipsilateral breast failures and that metastases can metastasize. American Journal of Clinical Pathology, 124(1), 49–57.
Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., & Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 100(7), 3983–3988.
Dalerba, P., Dylla, S. J., Park, I. K., et al. (2007). Phenotypic characterization of human colorectal cancer stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104(24), 10158–10163.
Hermann, P. C., Huber, S. L., 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(3), 313–323.
Lapidot, T., Sirard, C., Vormoor, J., et al. (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 367(6464), 645–648.
Li, C., Heidt, D. G., Dalerba, P., et al. (2007). Identification of pancreatic cancer stem cells. Cancer Research, 67(3), 1030–1037.
O’Brien, C. A., Pollett, A., Gallinger, S., & Dick, J. E. (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 445(7123), 106–110.
Ricci-Vitiani, L., Lombardi, D. G., Pilozzi, E., et al. (2007). Identification and expansion of human colon-cancer-initiating cells. Nature, 445(7123), 111–115.
Singh, S. K., Hawkins, C., Clarke, I. D., et al. (2004). Identification of human brain tumour initiating cells. Nature, 432(7015), 396–401.
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 Research, 67(9), 4010–4015.
Shmelkov, S. V., Butler, J. M., Hooper, A. T., et al. (2008). CD133 expression is not restricted to stem cells, and both CD133+ and CD133− metastatic colon cancer cells initiate tumors. Journal of Clinical Investigation, 118(6), 2111–2120.
Bonnet, D., & Dick, J. E. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Natural Medicine, 3(7), 730–737.
Cho, R. W., & Clarke, M. F. (2008). Recent advances in cancer stem cells. Current Opinion in Genetics & Development, 18(1), 48–53.
Vermeulen, L., Sprick, M. R., Kemper, K., Stassi, G., & Medema, J. P. (2008). Cancer stem cells—old concepts, new insights. Cell Death and Differentiation, 15(6), 947–958.
Dalerba, P., & Clarke, M. F. (2007). Cancer stem cells and tumor metastasis: first steps into uncharted territory. Cell Stem Cell, 1(3), 241–242.
Kaplan, R. N., Psaila, B., & Lyden, D. (2007). Niche-to-niche migration of bone-marrow-derived cells. Trends in Molecular Medicine, 13(2), 72–81.
Jordan, C. T. (2007). The leukemic stem cell. Best Pract Res Clin Haematol, 20(1), 13–18.
Adams, G. B., & Scadden, D. T. (2008). A niche opportunity for stem cell therapeutics. Gene Theraphy, 15(2), 96–99.
Lim, D. A., Huang, Y. C., & Alvarez-Buylla, A. (2007). The adult neural stem cell niche: lessons for future neural cell replacement strategies. Neurosurgery Clinic of North America, 18(1), 81–92, ix.
Sneddon, J. B., & Werb, Z. (2007). Location, location, location: the cancer stem cell niche. Cell Stem Cell, 1(6), 607–611.
Yilmaz, O. H., Valdez, R., Theisen, B. K., et al. (2006). Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature, 441(7092), 475–482.
Rajan, P., Panchision, D. M., Newell, L. F., & McKay, R. D. (2003). BMPs signal alternately through a SMAD or FRAP-STAT pathway to regulate fate choice in CNS stem cells. Journal of Cell Biology, 161(5), 911–921.
Piccirillo, S. G., Reynolds, B. A., Zanetti, N., et al. (2006). Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature, 444(7120), 761–765.
Cloughesy, T. F., Yoshimoto, K., Nghiemphu, P., et al. (2008). Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med, 5(1), 8.
Bild, A. H., Potti, A., & Nevins, J. R. (2006). Linking oncogenic pathways with therapeutic opportunities. Nature Reviews Cancer, 6(9), 735–741.
Roukos, D. H., Murray, S., & Briasoulis, E. (2007). Molecular genetic tools shape a roadmap towards a more accurate prognostic prediction and personalized management of cancer. Cancer Biol Ther, 6(3), 308–312.
Spisek, R., Kukreja, A., Chen, L. C., et al. (2007). Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy. Journal of Experimental Medicine, 204(4), 831–840.
Friedenson, B. (2007). The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers. BMC Cancer, 7, 152.
King, M. C., Marks, J. H., & Mandell, J. B. (2003). Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science, 302(5645), 643–646.
Levy, D. B., Smith, K. J., Beazer-Barclay, Y., Hamilton, S. R., Vogelstein, B., & Kinzler, K. W. (1994). Inactivation of both APC alleles in human and mouse tumors. Cancer Research, 54(22), 5953–5958.
Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., & Schreiber, R. D. (2002). Cancer immunoediting: from immunosurveillance to tumor escape. Nature Immunology, 3(11), 991–998.
Srinivasan, R., & Wolchok, J. D. (2004). Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines. Journal of Translational Medicine, 2(1), 12.
Finn, O. J. (2003). Premalignant lesions as targets for cancer vaccines. Journal of Experimental Medicine, 198(11), 1623–1626.
Hollingsworth, M. A., & Swanson, B. J. (2004). Mucins in cancer: protection and control of the cell surface. Nature Reviews Cancer, 4(1), 45–60.
Reis, C. A., David, L., Seixas, M., Burchell, J., & Sobrinho-Simoes, M. (1998). Expression of fully and under-glycosylated forms of MUC1 mucin in gastric carcinoma. International Journal of Cancer, 79(4), 402–410.
Yu, M., Zhan, Q., & Finn, O. J. (2002). Immune recognition of cyclin B1 as a tumor antigen is a result of its overexpression in human tumors that is caused by non-functional p53. Molecular Immunology, 38(12–13), 981–987.
Dhodapkar, M. V., Krasovsky, J., Osman, K., & Geller, M. D. (2003). Vigorous premalignancy-specific effector T cell response in the bone marrow of patients with monoclonal gammopathy. Journal of Experimental Medicine, 198(11), 1753–1757.
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Rajan, P., Srinivasan, R. Targeting Cancer Stem Cells in Cancer Prevention and Therapy. Stem Cell Rev 4, 211–216 (2008). https://doi.org/10.1007/s12015-008-9037-x
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DOI: https://doi.org/10.1007/s12015-008-9037-x