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Breast Cancer Biology for the Radiation Oncologist pp 49–57Cite as

Cancer Stem Cells and Radiotherapy

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Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

Abstract

In clinic, tumor recurrence and metastasis are the major barriers to further improve the overall cancer patients’ survival. The theory of tumor repopulation due to radiation described decades ago is being supported by new experimental data. The heterogeneity of cancer cell populations in a given tumor is recently evidenced by the present of cancer stem cells (CSCs) that are different from other non-CSC tumor cells and maintain unique self-renewal and tumor-initiating phenotypes. The CSCs isolated from many human tumors including the breast cancer stem cells (BCSCs) are demonstrated to hold specific characteristics and are demonstrated to be resistant to an array of anti-cancer agents and radiation therapy. In this chapter, a number of prosurvival pathways and biomarkers found in BCSCs will be discussed. Several prosurvival features including CSCs repopulation, DNA repair ability, as well as the HER2-NFκB-HER2 signaling loop in the radioresistant BCSCs will be illustrated. Further clarification of the specific networks associated with the radioresistant phenotype of BCSCs will shed new light on the molecular mechanism of tumor radioresistance, and will help to generate targets to detect and treat therapy-resistant tumor cells.

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References

  • Al-Hajj M (2007) Cancer stem cells and oncology therapeutics. Curr Opin Oncol 19:61–64

    PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Baldwin AS (1996) The NFkappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649–683

    Article  CAS  PubMed  Google Scholar 

  • Baldwin AS (2001) Control of oncogenesis and cancer therapy resistance by the transcription factor NFkappaB. J Clin Invest 107:241–246

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760

    Article  CAS  PubMed  Google Scholar 

  • Barkett M, Gilmore TD (1999) Control of apoptosis by Rel/NFkappaB transcription factors. Oncogene 18:6910–6924

    Article  CAS  PubMed  Google Scholar 

  • Baumann M, Krause M, Hill R (2008) Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer 8:545–554

    Article  CAS  PubMed  Google Scholar 

  • Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    Article  CAS  PubMed  Google Scholar 

  • Brach MA, Hass R, Sherman ML, Gunji H, Weichselbaum R, Kufe D (1991) Ionizing radiation induces expression and binding activity of the nuclear factor kappa B. J Clin Invest 88:691–695

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Britten CD (2004) Targeting ErbB receptor signaling: a pan-ErbB approach to cancer. Mol Cancer Ther 3:1335–1342

    CAS  PubMed  Google Scholar 

  • Cao N, Li S, Wang Z, Ahmed KM, Degnan ME, Fan M, Dynlacht JR, Li JJ (2009) NFkappaB-mediated HER2 overexpression in radiation-adaptive resistance. Radiat Res 171:9–21

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chang CJ, Hsu CC, Yung MC, Chen KY, Tzao C, Wu WF, Chou HY, Lee YY, Lu KH, Chiou SH, Ma HI (2009) Enhanced radiosensitivity and radiation-induced apoptosis in glioma CD133-positive cells by knockdown of SirT1 expression. Biochem Biophys Res Commun 380:236–242

    Article  CAS  PubMed  Google Scholar 

  • Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7:505–516

    Article  CAS  PubMed  Google Scholar 

  • Croker AK, Allan AL (2011). Inhibition of aldehyde dehydrogenase (ALDH) activity reduces chemotherapy and radiation resistance of stem-like ALDH(hi)CD44 (+) human breast cancer cells. Breast Cancer Res Treat. DOI 10.1007/s10549-10011-11692-y

  • Curry HA, Clemens RA, Shah S, Bradbury CM, Botero A, Goswami P, Gius D (1999) Heat shock inhibits radiation-induced activation of NFkappaB via inhibition of I-kappaB kinase. J Biol Chem 274:23061–23067

    Article  CAS  PubMed  Google Scholar 

  • Dalerba P, Cho RW, Clarke MF (2007) Cancer stem cells: models and concepts. Annu Rev Med 58:267–284

    Article  CAS  PubMed  Google Scholar 

  • Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219

    Article  CAS  PubMed  Google Scholar 

  • Diehn M, Cho RW, Clarke MF (2009) Therapeutic implications of the cancer stem cell hypothesis. Semin Radiat Oncol 19:78–86

    Article  PubMed Central  PubMed  Google Scholar 

  • Dolcet X, Llobet D, Pallares J, Matias-Guiu X (2005) NFkB in development and progression of human cancer. Virchows Arch 446:475–482

    Article  CAS  PubMed  Google Scholar 

  • Dylla SJ, Beviglia L, Park IK, Chartier C, Raval J, Ngan L, Pickell K, Aguilar J, Lazetic S, Smith-Berdan S, Clarke MF, Hoey T, Lewicki J, Gurney AL (2008) Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS ONE 3:e2428

    Article  PubMed Central  PubMed  Google Scholar 

  • Eccles SA (2001) The role of c-erbB-2/HER2/neu in breast cancer progression and metastasis. J Mammary Gland Biol Neoplasia 6:393–406

    Article  CAS  PubMed  Google Scholar 

  • Fan M, Ahmed KM, Coleman MC, Spitz DR, Li JJ (2007) Nuclear factor-kappaB and manganese superoxide dismutase mediate adaptive radioresistance in low-dose irradiated mouse skin epithelial cells. Cancer Res 67:3220–3228

    Article  CAS  PubMed  Google Scholar 

  • Feinendegen LE (1999) The role of adaptive responses following exposure to ionizing radiation. Hum Exp Toxicol 18:426–432

    Article  CAS  PubMed  Google Scholar 

  • Feinendegen LE (2002) Reactive oxygen species in cell responses to toxic agents. Hum Exp Toxicol 21:85–90

    Article  CAS  PubMed  Google Scholar 

  • Forrester HB, Albright N, Ling CC, Dewey WC (2000) Computerized video time-lapse analysis of apoptosis of REC:Myc cells X-irradiated in different phases of the cell cycle. Radiat Res 154:625–639

    Article  CAS  PubMed  Google Scholar 

  • Frosina G (2009) DNA repair in normal and cancer stem cells, with special reference to the central nervous system. Curr Med Chem 16:854–866

    Article  CAS  PubMed  Google Scholar 

  • Gilmore TD (2003) The Re1/NFkappa B/I kappa B signal transduction pathway and cancer. Cancer Treat Res 115:241–265

    Article  CAS  PubMed  Google Scholar 

  • Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Granville DJ, Carthy CM, Jiang H, Levy JG, McManus BM, Matroule JY, Piette J, Hunt DW (2000) Nuclear factor-kappaB activation by the photochemotherapeutic agent verteporfin. Blood 95:256–262

    CAS  PubMed  Google Scholar 

  • Guo G, Yan-Sanders Y, Lyn-Cook BD, Wang T, Tamae D, Ogi J, Khaletskiy A, Li Z, Weydert C, Longmate JA, Huang T-T, Spitz DR, Oberley LW, Li JJ (2003) Manganese superoxide dismutase-mediated gene expression in radiation-induced adaptive responses. Mol Cell Biol 23:2362–2378

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guo G, Wang T, Gao Q, Tamae D, Wong P, Chen T, Chen WC, Shively JE, Wong JY, Li JJ (2004) Expression of ErbB2 enhances radiation-induced NFkappaB activation. Oncogene 23:535–545

    Article  CAS  PubMed  Google Scholar 

  • Haffty BG, Brown F, Carter D, Flynn S (1996) Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: a case-control study. Int J Radiat Oncol Biol Phys 35:751–757

    Article  CAS  PubMed  Google Scholar 

  • Hambardzumyan D, Becher OJ, Rosenblum MK, Pandolfi PP, Manova-Todorova K, Holland EC (2008) PI3 K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes Dev 22:436–448

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hicks DG, Yoder BJ, Pettay J, Swain E, Tarr S, Hartke M, Skacel M, Crowe JP, Budd GT, Tubbs RR (2005) The incidence of topoisomerase II-alpha genomic alterations in adenocarcinoma of the breast and their relationship to human epidermal growth factor receptor-2 gene amplification: a fluorescence in situ hybridization study. Hum Pathol 36:348–356

    Article  CAS  PubMed  Google Scholar 

  • Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF, Hynes NE (2003) The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A 100:8933–8938

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL (2008) CD44+ CD24(−) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer 98:756–765

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jiang Z, Pore N, Cerniglia GJ, Mick R, Georgescu MM, Bernhard EJ, Hahn SM, Gupta AK, Maity A (2007) Phosphatase and tensin homologue deficiency in glioblastoma confers resistance to radiation and temozolomide that is reversed by the protease inhibitor nelfinavir. Cancer Res 67:4467–4473

    Article  CAS  PubMed  Google Scholar 

  • Johannessen TC, Bjerkvig R, Tysnes BB (2008) DNA repair and cancer stem-like cells–potential partners in glioma drug resistance? Cancer Treat Rev 34:558–567

    Article  CAS  PubMed  Google Scholar 

  • Jung M, Dritschilo A (2001) NFkappa B signaling pathway as a target for human tumor radiosensitization. Semin Radiat Oncol 11:346–351

    Article  CAS  PubMed  Google Scholar 

  • Jung M, Zhang Y, Lee S, Dritschilo A (1995) Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha. Science 268:1619–1621

    Article  CAS  PubMed  Google Scholar 

  • Jung M, Zhang Y, Dritschilo A (1997) Expression of a dominant negative I kappa B-alpha modulates hypersensitivity of ataxia telangiectasia fibroblasts to streptonigrin-induced apoptosis. Radiat Oncol Investig 5:265–268

    Article  CAS  PubMed  Google Scholar 

  • Karin M (2006) NFkappaB and cancer: mechanisms and targets. Mol Carcinog 45:355–361

    Article  CAS  PubMed  Google Scholar 

  • Kataoka Y, Murley JS, Khodarev NN, Weichselbaum RR, Grdina DJ (2002) Activation of the nuclear transcription factor kappaB (NFkappaB) and differential gene expression in U87 glioma cells after exposure to the cytoprotector amifostine. Int J Radiat Oncol Biol Phys 53:180–189

    Article  CAS  PubMed  Google Scholar 

  • Kelsey KT, Memisoglu A, Frenkel D, Liber HL (1991) Human lymphocytes exposed to low doses of X-rays are less susceptible to radiation-induced mutagenesis. Mutat Res 263:197–201

    Article  CAS  PubMed  Google Scholar 

  • Kim JJ, Tannock IF (2005) Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer 5:516–525

    Article  CAS  PubMed  Google Scholar 

  • Korkaya H, Paulson A, Iovino F, Wicha MS (2008) HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27:6120–6130

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kucharczak J, Simmons MJ, Fan Y, Gelinas C (2003) To be, or not to be: NFkappaB is the answer—role of Rel/NFkappaB in the regulation of apoptosis. Oncogene 22:8961–8982

    Article  CAS  PubMed  Google Scholar 

  • Kurokawa H, Arteaga CL (2001) Inhibition of erbB receptor (HER) tyrosine kinases as a strategy to abrogate antiestrogen resistance in human breast cancer. Clin Cancer Res 7:4442

    Google Scholar 

  • Lacroix M (2006) Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer 13:1033–1067

    Article  CAS  PubMed  Google Scholar 

  • Lavon I, Fuchs D, Zrihan D, Efroni G, Zelikovitch B, Fellig Y, Siegal T (2007) Novel mechanism whereby nuclear factor kappaB mediates DNA damage repair through regulation of O(6)-methylguanine-DNA-methyltransferase. Cancer Res 67:8952–8959

    Article  CAS  PubMed  Google Scholar 

  • Lenardo MJ, Baltimore D (1989) NFkappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell 58:227–229

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Verma IM (2002) NFkappaB regulation in the immune system. Nat Rev Immunol 2:725–734

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Xia L, Lee ML, Khaletskiy A, Wang J, Wong JYC, Li JJ (2001) Effector genes altered in MCF-7 human breast cancer cells after exposure to fractionated ionizing radiation. Radiat Res 155:543–553

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Wang H, Eyler CE, Hjelmeland AB, Rich JN (2009) Turning cancer stem cells inside out: an exploration of glioma stem cell signaling pathways. J Biol Chem 284:16705–16709

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liang K, Lu Y, Jin W, Ang KK, Milas L, Fan Z (2003a) Sensitization of breast cancer cells to radiation by trastuzumab. Mol Cancer Ther 2:1113–1120

    CAS  PubMed  Google Scholar 

  • Liang K, Jin W, Knuefermann C, Schmidt M, Mills GB, Ang KK, Milas L, Fan Z (2003b) Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy. Mol Cancer Ther 2:353–360

    CAS  PubMed  Google Scholar 

  • Locke JE, Bradbury CM, Wei SJ, Shah S, Rene LM, Clemens RA, Roti Roti J, Horikoshi N, Gius D (2002) Indomethacin lowers the threshold thermal exposure for hyperthermic radiosensitization and heat-shock inhibition of ionizing radiation-induced activation of NFkappaB. Int J Radiat Biol 78:493–502

    Article  CAS  PubMed  Google Scholar 

  • Luo J-L, Kamata H, Karin M (2005) IKK/NFkappaB signaling: balancing life and death—a new approach to cancer therapy. J Clin Invest 115:2625–2632

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Maity A, Kao GD, Muschel RJ, McKenna WG (1997) Potential molecular targets for manipulating the radiation response. Int J Radiat Oncol Biol Phys 37:639–653

    Article  CAS  PubMed  Google Scholar 

  • Margison GP, Povey AC, Kaina B, Santibanez Koref MF (2003) Variability and regulation of O6-alkylguanine-DNA alkyltransferase. Carcinogenesis 24:625–635

    Article  CAS  PubMed  Google Scholar 

  • Olayioye MA (2001) Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members. Breast Cancer Res 3:385–389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Olivieri G, Bodycote J, Wolff S (1984) Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science 223:594–597

    Article  CAS  PubMed  Google Scholar 

  • Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3:895–902

    Article  CAS  PubMed  Google Scholar 

  • Phillips TM, McBride WH, Pajonk F (2006) The response of CD24(−/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 98:1777–1785

    Article  PubMed  Google Scholar 

  • Pianetti S, Arsura M, Romieu-Mourez R, Coffey RJ, Sonenshein GE (2001) Her-2/neu overexpression induces NFkappaB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IkappaB-alpha that can be inhibited by the tumor suppressor PTEN. Oncogene 20:1287–1299

    Article  CAS  PubMed  Google Scholar 

  • Pietras RJ, Poen JC, Gallardo D, Wongvipat PN, Lee HJ, Slamon DJ (1999) Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 59:1347–1355

    CAS  PubMed  Google Scholar 

  • Prieur-Carrillo G, Chu K, Lindqvist J, Dewey WC (2003) Computerized video time-lapse (CVTL) analysis of the fate of giant cells produced by X-irradiating EJ30 human bladder carcinoma cells. Radiat Res 159:705–712

    Article  CAS  PubMed  Google Scholar 

  • Puc J, Keniry M, Li HS, Pandita TK, Choudhury AD, Memeo L, Mansukhani M, Murty VV, Gaciong Z, Meek SE, Piwnica-Worms H, Hibshoosh H, Parsons R (2005) Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell 7:193–204

    Article  CAS  PubMed  Google Scholar 

  • Rich JN (2007) Cancer stem cells in radiation resistance. Cancer Res 67:8980–8984

    Article  CAS  PubMed  Google Scholar 

  • Robson T, Price ME, Moore ML, Joiner MC, McKelvey-Martin VJ, McKeown SR, Hirst DG (2000) Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance. Int J Radiat Biol 76:617–623

    Article  CAS  PubMed  Google Scholar 

  • Romashkova JA, Makarov SS (1999) NFkappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 401:86–90

    Article  CAS  PubMed  Google Scholar 

  • Schmidt-Ullrich RK, Dent P, Grant S, Mikkelsen RB, Valerie K (2000) Signal transduction and cellular radiation responses. Radiat Res 153:245–257

    Article  CAS  PubMed  Google Scholar 

  • Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R, Badve S, Nakshatri H (2006). CD44+/CD24− breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res 8:R59

    Article  Google Scholar 

  • Skov KA (1999) Perspectives on the adaptive response from studies on the response to low radiation doses (or to cisplatin) in mammalian cells. Hum Exp Toxicol 18:447–451

    Article  CAS  PubMed  Google Scholar 

  • Skvortsova   (2008) Intracellular signaling pathways regulating radioresistance of human prostate carcinoma cells. Proteomics 8:4521–4533

    Article  CAS  PubMed  Google Scholar 

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    Article  CAS  PubMed  Google Scholar 

  • Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    Article  CAS  PubMed  Google Scholar 

  • Soomro S, Shousha S, Taylor P, Shepard HM, Feldmann M (1991) c-erbB-2 expression in different histological types of invasive breast carcinoma. J Clin Pathol 44:211–214

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Spitz DR, Azzam EI, Li JJ, Gius D (2004) Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metastasis Rev 23:311–322

    Article  CAS  PubMed  Google Scholar 

  • Stecca C, Gerber GB (1998) Adaptive response to DNA-damaging agents: a review of potential mechanisms. Biochem Pharmacol 55:941–951

    Article  CAS  PubMed  Google Scholar 

  • Stockler M, Wilcken NR, Ghersi D, Simes RJ (2000) Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer. Cancer Treat Rev 26:151–168

    Article  CAS  PubMed  Google Scholar 

  • Summers RW, Maves BV, Reeves RD, Arjes LJ, Oberley LW (1989) Irradiation increases superoxide dismutase in rat intestinal smooth muscle. Free Radic Biol Med 6:261–270

    Article  CAS  PubMed  Google Scholar 

  • Suzuki K, Kodama S, Watanabe M (1998) Suppressive effect of low-dose preirradiation on genetic instability induced by X rays in normal human embryonic cells. Radiat Res 150:656–662

    Article  CAS  PubMed  Google Scholar 

  • Suzuki K, Kodama S, Watanabe M (2001) Extremely low-dose ionizing radiation causes activation of mitogen-activated protein kinase pathway and enhances proliferation of normal human diploid cells. Cancer Res 61:5396–5401

    CAS  PubMed  Google Scholar 

  • Tang G, Minemoto Y, Dibling B, Purcell NH, Li Z, Karin M, Lin A (2001) Inhibition of JNK activation through NFkappaB target genes. Nature 414:313–317

    Article  CAS  PubMed  Google Scholar 

  • Uno M, Otsuki T, Kurebayashi J, Sakaguchi H, Isozaki Y, Ueki A, Yata K, Fujii T, Hiratsuka J, Akisada T, Harada T, Imajo Y (2001) Anti-HER2-antibody enhances irradiation-induced growth inhibition in head and neck carcinoma. Int J Cancer 94:474–479

    Article  CAS  PubMed  Google Scholar 

  • Valabrega G, Montemurro F, Aglietta M (2007) Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol 18:977–984

    Article  CAS  PubMed  Google Scholar 

  • Waldman T, Zhang Y, Dillehay L, Yu J, Kinzler K, Vogelstein B, Williams J (1997) Cell-cycle arrest versus cell death in cancer therapy. Nat Med 3:1034–1036

    Article  CAS  PubMed  Google Scholar 

  • Warren CM, Landgraf R (2006) Signaling through ERBB receptors: multiple layers of diversity and control. Cell Signal 18:923–933

    Article  CAS  PubMed  Google Scholar 

  • Weichselbaum RR, Hallahan D, Fuks Z, Kufe D (1994) Radiation induction of immediate early genes: effectors of the radiation-stress response. Int J Radiat Oncol Biol Phys 30:229–234

    Article  CAS  PubMed  Google Scholar 

  • Wolff S (1989) Are radiation-induced effects hormetic? Science 245:575

    Article  CAS  PubMed  Google Scholar 

  • Wolff S (1998) The adaptive response in radiobiology: evolving insights and implications. Environ Health Perspect 106(Suppl 1):277–283

    Article  PubMed Central  PubMed  Google Scholar 

  • Yang HY, Zhou BP, Hung MC, Lee MH (2000) Oncogenic signals of HER-2/neu in regulating the stability of the cyclin-dependent kinase inhibitor p27. J Biol Chem 275:24735–24739

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, University of California Davis, 4501 X Street, Sacramento, CA, 95817, USA

    Jian Jian Li

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  1. Department of Radiation Oncology, Northwestern University, Chicago, Illinois, USA

    Jonathan Strauss

  2. Division of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Chicago, Illinois, USA

    William Small

  3. Dept. Radiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

    Gayle E. Woloschak

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Li, J.J. (2012). Cancer Stem Cells and Radiotherapy. In: Strauss, J., Small, W., Woloschak, G. (eds) Breast Cancer Biology for the Radiation Oncologist. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2012_648

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