Skip to main content
SpringerLink
Log in

Cancer Stem Cells and Their Therapeutic Applications

  • Chapter
  • First Online:
Stem Cells for Cancer and Genetic Disease Treatment

Part of the book series: Stem Cells in Clinical Applications ((SCCA))

  • 694 Accesses

Abstract

Cancer is currently a major health problem that impacts human life worldwide. Several studies support the concept of stem cells in cancerogenesis. The cancer stem cell (CSC) population is tumorigenic and displays characteristic markers and properties of stem cells, including self- renewal/proliferation and differentiation. CSCs can play an important role in carcinogenesis. Many therapeutic strategies currently focus on ablating the subpopulation of CSCs using different approaches such as the overcoming of CSC resistance mechanisms or targeting key molecular pathways controlling these cells. Although these therapeutic strategies have few reported side effects, new strategies are still needed. In this chapter, we describe accumulated data on the stem cell concept of cancerogenesis, how dysregulation of stem cell self-renewal affects cancer transformation, and the roles of CSCs in cancer therapy. We also discuss how improving our current understanding of the biology, behavior, and environment of CSCs can help in advancing their applications in cancer therapies, and devising more effective therapeutic strategies and approaches for cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AML:

Acute myelogenous leukemia

BMPs:

Bone morphogenetic proteins

CML:

Chronic myelogenous leukemia

CSCs:

Cancer stem cells

EMT:

Epithelial-mesenchymal transition

HSCs:

Hematopoietic stem cells

Sca-1:

Stem cell antigen-1

VEGF:

Vascular endothelial growth factor

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 U S A 100:3983–3988

    Article  CAS  Google Scholar 

  • Al-Hajj M, Becker MW, Wicha M, Weissman IL, Clarke MF (2004) Therapeutic implications of cancer stem cells. Curr Opin Genet Dev 14:43–47

    Article  CAS  Google Scholar 

  • Aponte PM, Caicedo A (2017) Stemness in cancer: stem cells, cancer stem cells, and their microenvironment. Stem Cells Intl 2017:1–17

    Article  Google Scholar 

  • Atena M, Reza AM, Mehran G (2014) A review on the biology of cancer stem cells. Stem Cell Discov 4:83–89

    Article  Google Scholar 

  • Batlle E, Clevers H (2017) Cancer stem cells revisited. Nat Med 23:1124–1134

    Article  CAS  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  Google Scholar 

  • Benson RA, Lowrey JA, Lamb JR, Howie SE (2004) The Notch and Sonic hedgehog signalling pathways in immunity. Mol Immunol 41:715–725

    Article  CAS  Google Scholar 

  • Blagosklonny MV (2006) Target for cancer therapy: proliferating cells or stem cells. Leukemia 20:385–391

    Article  CAS  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  Google Scholar 

  • Bao S, Wu Q, Sathornsumetee S et al (2006 August 15) Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66(16):7843–7848

    Article  CAS  Google Scholar 

  • Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ et al (2013) Acquisition of epithelial–mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance. Cell Death Dis 4:875–884

    Article  Google Scholar 

  • Cho K, Wang X, Nie S, Chen ZG, Shin DM (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14:1310–1316

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284

    Article  CAS  Google Scholar 

  • Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN et al (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458:780–783

    Article  CAS  Google Scholar 

  • Dievart A, Beaulieu N, Jolicoeur P (1999) Involvement of Notch1 in the development of mouse mammary tumors. Oncogene 18:5973–5981

    Article  CAS  Google Scholar 

  • Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS (2003) Stem cells in normal breast development and breast cancer. Cell Prolif 36:59–72

    Article  CAS  Google Scholar 

  • Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS (2004) Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res 6:605–615

    Article  Google Scholar 

  • Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira S-M, García-Echeverría C et al (2009) The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci U S A 106(1):268–273

    Article  CAS  Google Scholar 

  • Eyler CE, Rich JN (2008) Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol 26:2839–2845

    Article  CAS  Google Scholar 

  • Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E et al (1999) A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood 94:1192–1200

    CAS  PubMed  Google Scholar 

  • Formelli F, Cleris L (1993) Synthetic retinoid fenretinide is effective against a human ovarian carcinoma xenograft and potentiates cisplatin activity. Cancer Res 53:5374–5376

    CAS  PubMed  Google Scholar 

  • Francipane MG, Alea MP, Lombardo Y, Todaro M, Medema JP, Stassi G (2008) Crucial role of interleukin-4 in the survival of colon cancer stem cells. Cancer Res 68:4022–4025

    Article  CAS  Google Scholar 

  • Gal H, Makovitzki A, Amariglio N, Rechavi G, Ram Z, Givol D (2007) A rapid assay for drug sensitivity of glioblastoma stem cells. Biochem Biophys Res Commun 358:908–913

    Article  CAS  Google Scholar 

  • Gil J, Stembalska A, Pesz KA, Sasiadek MM (2008) Cancer stem cells: the theory and perspectives in cancer therapy. J App Genet 49:193–199

    Article  Google Scholar 

  • Gupta PB, Fillmore CM, Jiang G, Shapira SD, Tao K, Kuperwasser C et al (2011) Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell 146:633–644

    Article  CAS  Google Scholar 

  • Hambardzumyan D, Becher OJ, Rosenblum MK, Pandolfi PP, Manova-Todorova K, Holland EC (2008) PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes Dev 22:436–448

    Article  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  Google Scholar 

  • Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5:738–743

    Article  CAS  Google Scholar 

  • Ito K, Suda T (2014) Metabolic requirements for the maintenance of self-renewing stem cells. Nat Rev Mol Cell Biol 15(4):243–256

    Article  CAS  Google Scholar 

  • Jamieson C, Ailles L, Dylla S et al (2004) Granulocyte macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 351:657–667

    Article  CAS  Google Scholar 

  • Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12:1167–1174

    Article  Google Scholar 

  • Karhadkar SS, Bova GS, Abdallah N et al (2004) Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 431:707–712

    Article  CAS  Google Scholar 

  • Kelly LM, Gilliland DG (2002) Genetics of myeloid leukemias. Annu Rev Genomics Hum Genet 3:179–198

    Article  CAS  Google Scholar 

  • Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS et al (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844

    Article  CAS  Google Scholar 

  • Kim CF, Jackson EL, Woolfenden AE et al (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121:823–835

    Article  CAS  Google Scholar 

  • Krause DS, Lazarides K, von Andrian UH, Van Etten RA (2006) Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nat Med 12:1175–1180

    Article  CAS  Google Scholar 

  • Kreso A et al (2014) Evolution of the cancer stem cell model. Cell Stem Cell 14(3):275–291

    Article  CAS  Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J et al (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367:645–648

    Article  CAS  Google Scholar 

  • Linkous AG, Yazlovitskaya EM (2012) Novel radiosensitizing anticancer therapeutics. Anticancer Res 32:2487–2499

    CAS  PubMed  Google Scholar 

  • Liu S, Dontu G, Wicha MS (2005) Mammary stem cells, selfrenewal pathways, and carcinogenesis. Breast Cancer Res 7:86–95

    Article  CAS  Google Scholar 

  • Liu C, Zhao G, Liu J et al (2009) Novel biodegradable lipid nano complex for siRNA delivery significantly improving the chemosensitivity of human colon cancer stem cells to paclitaxel. J Control Release 140:277–283

    Article  CAS  Google Scholar 

  • Munro MJ, Wickremesekera SK, Peng L et al (2018) Cancer stem cells in colorectal cancer: a review. J Clin Pathol 71:110–116

    Article  CAS  Google Scholar 

  • Nam Y, Aster JC, Blacklow SC (2002) Notch signaling as a therapeutic target. Curr Opin Chem Biol 6:501–509

    Article  CAS  Google Scholar 

  • Nassar D, Blanpain C (2016) Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol 11:47–76

    Article  CAS  Google Scholar 

  • Nickoloff BJ, Osborne BA, Miele L (2003) Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents. Oncogene 22:6598–6608

    Article  CAS  Google Scholar 

  • Papaccio F, Paino F, Regad T, Papaccio G, Desiderio V, Tirino V (2017) Concise review: cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Transl Med 6(12):2115–2125

    Article  Google Scholar 

  • Pece S, Serresi M, Santolini E et al (2004) Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol 167:215–221

    Article  CAS  Google Scholar 

  • Pecqueur C, Oliver L, Oizel K, Lalier L, Vallette FM (2013) Targeting metabolism to induce cell death in cancer cells and cancer stem cells. Int J Cell Biol 2013:805975

    Google Scholar 

  • Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G et al (2006) Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444:761–765

    Article  CAS  Google Scholar 

  • Plate KH, Breier G, Weich HA, Risau W (1992) Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359:845–848

    Article  CAS  Google Scholar 

  • Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R et al (2009) Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 4:568–580

    Article  CAS  Google Scholar 

  • Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65:5506–5511

    Article  CAS  Google Scholar 

  • Potiron VA et al (2013) Radiosensitization of prostate cancer cells by the dual PI3K/mTOR inhibitor BEZ235 under normoxic and hypoxic conditions. Radiother Oncol 106:138–146

    Article  CAS  Google Scholar 

  • Qin W, Huang G, Chen Z, Zhang Y (2017) Nanomaterials in targeting cancer stem cells for cancer therapy. Front Pharmacol 8:1–15

    PubMed  PubMed Central  Google Scholar 

  • Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ (2008) Efficient tumour formation by single human melanoma cells. Nature 456:593–598

    Article  CAS  Google Scholar 

  • Reisfeld RA (2013) The tumor microenvironment: a target for combination therapy of breast cancer. Crit Rev Oncog 18:115–133

    Article  Google Scholar 

  • Ricci-Vitiani L, Lombardi DG, Pilozzi E et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445:111–115

    Article  CAS  Google Scholar 

  • Rich JN, Bao S (2007) Chemotherapy and cancer stem cells. Cell Stem Cell 1:353–355

    Article  CAS  Google Scholar 

  • Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT (2004) CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 117:1539–1545

    Article  Google Scholar 

  • Romer JT, Kimura H, Magdaleno S et al (2004) Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/_)p53(_/_) mice. Cancer Cell 6:229–240

    Article  CAS  Google Scholar 

  • Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843–850. https://doi.org/10.1038/nature03319

    Article  CAS  Google Scholar 

  • Shen S, Xia J-X, Wang J (2016) Nanomedicine-mediated cancer stem cell therapy. Biomaterials 74:1e18

    Article  Google Scholar 

  • Shigdar S, Lin J, Li Y, Yang CJ, Wei M, Zhus Y et al (2012) Cancer stem cell targeting: the next generation of cancer therapy and molecular imaging. Ther Deliv 3:227–244

    Article  CAS  Google Scholar 

  • Shkembi E, Daniele N, Zinno F, Omar GE (2016) Cancer stem cells and nanomedicine. Peertechz J Cytol Pathol 1(1):048–053

    Google Scholar 

  • Singh SK, Clarke ID, Hide T, Dirks PB (2004a) Cancer stem cells in nervous system tumors. Oncogene 23:7267–7273

    Article  CAS  Google Scholar 

  • Singh S, Hawkins C, Clarke I et al (2004b) Identification of human brain tumour initiating cells. Nature 432:396–401

    Article  CAS  Google Scholar 

  • Siziopikou K, Miao H, Rizzo P et al (2003) Notch signaling is a therapeutic target in breast cancer. In: Proceedings of the 94th annual meeting of the AACR. pp 1277–1278

    Google Scholar 

  • Soeda A, Inagaki A, Oka N, Ikegame Y, Aoki H, Yoshimura S et al (2008) Epidermal growth factor plays a crucial role in mitogenic regulation of human brain tumor stem cells. J Biol Chem 283:10958–10966

    Article  CAS  Google Scholar 

  • Tang DG (2012) Understanding cancer stem cell heterogeneity and plasticity. Cell Res 22:457–472

    Article  CAS  Google Scholar 

  • Unden AB, Holmberg E, Lundh-Rozell B et al (1996) Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the Gorlin syndrome: different in vivo mechanisms of PTCH inactivation. Cancer Res 56:4562–4565

    CAS  PubMed  Google Scholar 

  • Weijzen S, Rizzo P, Braid M et al (2002) Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med 8:979–986

    Article  CAS  Google Scholar 

  • Williams DA, Cancelas JA (2006) Leukaemia: niche retreats for stem cells. Nature 444:827–828

    Article  CAS  Google Scholar 

  • Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM (2007) WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci U S A 104:618–623

    Article  CAS  Google Scholar 

  • Yang X, Zhang X, Fu ML, Weichselbaum RR, Gajewski TF, Guo Y et al (2014) Targeting the tumor microenvironment with interferon-bridges innate and adaptive immune responses. Cancer Cell 25:37–48

    Article  Google Scholar 

  • Zhu Y, Ghosh P, Charnay P, Burns DK, Prada LF (2002) Nuerofibromas in NF1. Schwann cell origin and role of tumor environment. Science 296:920–922

    Article  CAS  Google Scholar 

  • Zieker D, Bühler S, Ustündag Z, Königsrainer I, Manncke S, Bajaeifer K et al (2013) Induction of tumor stem cell differentiation—novel strategy to overcome therapy resistance in gastric cancer. Langenbecks Arch Surg Dtsch Ges Für Chir 398:603–608

    Article  Google Scholar 

Download references

Conflict of Interest

The author confirms that this book contents have no conflict of interest.

Author information

Authors and Affiliations

  1. Centre for Biomedical Sciences Education, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland, UK

    Eiman Abdel Meguid

  2. The University of Edinburgh-Zhejiang International campus (UoE-ZJU Institute), and Centre of Stem Cell and Regenerative Medicine, Schools of Medicine & Basic Medicine, Zhejiang University, Haining, Zhejiang, China

    Ahmed El-Hashash

  3. The University of Edinburgh-Zhejiang International Campus, (UoE-ZJU), Arts and Science Building, Haining, Zhejiang, China

    Ahmed El-Hashash

Authors
  1. Eiman Abdel Meguid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmed El-Hashash
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Laboratory of Stem Cell Research and Application & Stem Cell Institute & Cancer Research Laboratory, VNUHCM University of Science, Ho Chi Minh City, Vietnam

    Phuc Van Pham

  2. University of Edinburgh - Zhejiang, International Campus (UoE-ZJU), Haining, Zhejiang, China

    Ahmed El-Hashash

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Meguid, E.A., El-Hashash, A. (2018). Cancer Stem Cells and Their Therapeutic Applications. In: Pham, P., El-Hashash, A. (eds) Stem Cells for Cancer and Genetic Disease Treatment. Stem Cells in Clinical Applications. Springer, Cham. https://doi.org/10.1007/978-3-319-98065-2_1

Download citation

Publish with us

Policies and ethics

Search

Navigation