Targeted Cancer Stem Cell Therapy

  • Mirjana Pavlovic
  • Bela Balint


The concept of cancer stem cells has been a compelling but controversial idea for many years. It suggests that at the root of any cancer there is a small subset of cancer cells that are solely responsible for driving the growth and evolution of a patient’s cancer. These cancer stem cells replenish themselves and produce the other types of cancer cells, as normal stem cells produce other normal tissues. The concept is important, because it suggests that only by developing treatments that get rid of the cancer stem cells will you be able to eradicate the cancer. Likewise, if you could selectively eliminate these cancer stem cells, the other remaining cancer cells would not be able to sustain the cancer. This chapter will summarize the novelties in cancer treatment that would be able to target specifically cancer stem cells.


Stem Cell Cancer Stem Cell Osteoporosis Drug Ovarian Clear Cell Carcinoma Target Cancer Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Santini JT Jr, Cima MJ, Langer R (1999) A controlled-release microchip. Nature 397:335–338CrossRefGoogle Scholar
  2. 2.
    Yang T, Rycaj K (2015) Targeted therapy against cancer stem cells (review). Oncol Lett 10:27–33Google Scholar
  3. 3.
    Timko BP, Arruebo M, Shankarappa SA, McAlvin JB, Okonkwo OS, Mizrahi B, Stefanescu CF, Gomez L, Zhu J, Zhu A, Santamaria J, Langer R, Kohane DS (2014) Near infrared-actuated devices for remotely controlled drug delivery. Proc Natl Acad Sci U S A 111(4):1349–1354CrossRefGoogle Scholar
  4. 4.
    Guduru R, Liang P, Runowicz C, Nair M, Atluri V, Khizroev S (2013) Magneto-electric nanoparticles (MENs) to enable field-controlled high-specificity drug delivery to eradicate ovarian cancer cells. Sci Rep 3:2953CrossRefGoogle Scholar
  5. 5.
    De Jong WH, De Borm PJA (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine 3(2):133–149CrossRefGoogle Scholar
  6. 6.
  7. 7.
    Rao W, Wang H, Han J, Zhao S, Dumbleton J, Agarwal P, Zhang W, Zhao G, Yu J, Zynger DL, Lu X, He X (2015) Chitosan-decorated doxorubicin-encapsulated nanoparticle targets and eliminates tumor reinitiating cancer stem-like cells. ACS Nano 9(6):5725. doi: 10.1021/nn506928p CrossRefGoogle Scholar
  8. 8.
    Cirillo G, Iemma F, Puoci F, Parisi OI, Curcio M, Spizzirri UG, Picci N (2009) Imprinted hydrophilic nanospheres as drug delivery systems for 5-fluorouracil sustained release. J Drug Target 17(1):72–77CrossRefGoogle Scholar
  9. 9.
    Cirillo G, Hampel S, Spizzirri GU, Paris O, Picci N, Iemma F (2014) Carbon nanotubes hybrid hydrogels in drug delivery: a perspective review. Biomed Res Int 2014:825017CrossRefGoogle Scholar
  10. 10.
    Daum N, Tscheka C, Neumeyer A, Schneider M (2012) Novel approaches for drug delivery systems in nanomedicine: effects of particle design and shape. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4(1):52–65CrossRefGoogle Scholar
  11. 11.
    Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 56(11):1649–1659CrossRefGoogle Scholar
  12. 12.
    Davis ME (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7(9):771–782CrossRefGoogle Scholar
  13. 13.
    Farokhzad OC et al (2004) Nanoparticle-aptamer bioconjugates a new approach for targeting prostate cancer cells. Cancer Res 64(21):7668–7672CrossRefGoogle Scholar
  14. 14.
    Hapira A, Livney YD, Broxterman HJ, Assaraf YG (2011) Nanomedicine for targeted cancer therapy: towards the overcoming of drug resistance. Drug Resist Updat 14:150–163CrossRefGoogle Scholar
  15. 15.
    Gil J, Stembalska A, Pesz KA, Sasiadek MM (2008) Cancer stem cells: the theory and perspectives in cancer therapy. J Appl Genet 49(2):193–199CrossRefGoogle Scholar
  16. 16.
    Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O’Shaughnessy J (2005) Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 23(31):7794–7803CrossRefGoogle Scholar
  17. 17.
    Hapira A, Livney YD, Broxterman HJ, Assaraf YG (2011) Nanomedicine for targeted cancer therapy: towards the overcoming of drug resistance. Drug Resist Updat 14:150–163CrossRefGoogle Scholar
  18. 18.
    Ahmed N, Fessi H, Elaissari A (2012) Theranostic applications of nanoparticles in cancer. Drug Discov Today 17(17–18):928–934CrossRefGoogle Scholar
  19. 19.
    Vinogradov S, Wei X (2012) Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine (Lond) 7:597–615CrossRefGoogle Scholar
  20. 20.
    Lim KJ, Bisht S, Bar EE, Maitra A, Eberhart CG (2011) A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors. Cancer Biol Ther 11:464–473CrossRefGoogle Scholar
  21. 21.
    Zhou BBS, Zhang H, Damelin M, Geles KG, Grindley JC et al (2009) Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 8:806–823CrossRefGoogle Scholar
  22. 22.
    McDermott SP, Wicha MS (2010) Targeting breast cancer stem cells. Mol Oncol 4:404–419CrossRefGoogle Scholar
  23. 23.
    Wu X, Chen H, Wang X (2012) Can lung cancer stem cells be targeted for therapies? Cancer Treat Rev 38:580–588CrossRefGoogle Scholar
  24. 24.
    Mamaeva V, Rosenholm JM, Bate-Eya LT, Bergman L, Peuhu E et al (2011) Mesoporous silica nanoparticles as drug delivery systems for targeted inhibition of Notch signaling in cancer. Mol Ther 19:1538–1546CrossRefGoogle Scholar
  25. 25.
    Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC et al (2008) Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 13:153–166CrossRefGoogle Scholar
  26. 26.
    Liu C, Zhao G, Liu J, Ma N, Chivukula P 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 140:277–283CrossRefGoogle Scholar
  27. 27.
    Bader AG, Brown D, Stoudemire J, Lammers P (2011) Developing therapeutic microRNAs for cancer. Gene Ther 18:1121–1126CrossRefGoogle Scholar
  28. 28.
    Piao L, Zhang M, Datta J, Xie X, Su T et al (2012) Lipid-based nanoparticle delivery of pre-miR-107 inhibits the tumorigenicity of head and neck squamous cell carcinoma. Mol Ther 20:1261–1269CrossRefGoogle Scholar
  29. 29.
    Yin D, Ogawa S, Kawamata N, Leiter A, Ham M et al (2013) miR-34a Functions as a tumor suppressor modulating EGFR in glioblastoma multiforme. Oncogene 32(9):1155–1163CrossRefGoogle Scholar
  30. 30.
    Ugras S, Brill E, Jacobsen A, Hafner M, Socci ND et al (2011) Small RNA sequencing and functional characterization reveals MicroRNA-143 tumor suppressor activity in liposarcoma. Cancer Res 71:5659–5669CrossRefGoogle Scholar
  31. 31.
    Pramanik D, Campbell NR, Karikari C, Chivukula R, Kent OA et al (2011) Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice. Mol Cancer Ther 10:1470–1480CrossRefGoogle Scholar
  32. 32.
    Issels RD (2008) Hyperthermia adds to chemotherapy. Eur J Cancer 44:2546–2554CrossRefGoogle Scholar
  33. 33.
    Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B et al (2003) Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc Natl Acad Sci U S A 100:13549–13554CrossRefGoogle Scholar
  34. 34.
    Yang K, Zhang S, Zhang G, Sun X, Lee ST et al (2010) Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett 10:3318–3323CrossRefGoogle Scholar
  35. 35.
    Kam NW, O’Connell M, Wisdom JA, Dai H (2005) Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci U S A 102:11600–11605CrossRefGoogle Scholar
  36. 36.
    Burke A, Ding X, Singh R, Kraft RA, Levi-Polyachenko N et al (2009) Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation. Proc Natl Acad Sci U S A 106:12897–12902CrossRefGoogle Scholar
  37. 37.
    Ding X, Singh R, Burke A, Hatcher H, Olson J et al (2011) Development of iron-containing multiwalled carbon nanotubes for MR-guided laser-induced thermotherapy. Nanomedicine (Lond) 6:1341–1352CrossRefGoogle Scholar
  38. 38.
    Huang X, El-Sayed IH, Qian W, El-Sayed MA (2006) Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 128:2115–2120CrossRefGoogle Scholar
  39. 39.
    Burke AR, Singh RN, Carroll DL, Wood JC, D’Agostino RB et al (2012) The resistance of breast cancer stem cells to conventional hyperthermia and their sensitivity to nanoparticle-mediated photothermal therapy. Biomaterials 33:2961–2970CrossRefGoogle Scholar
  40. 40.
    Atkinson RL, Zhang M, Diagaradjane P, Peddibhotla S, Contreras A et al (2010) Thermal enhancement with optically activated gold nanoshells sensitizes breast cancer stem cells to radiation therapy. Sci Transl Med 2:55–79CrossRefGoogle Scholar
  41. 41.
    Phillips TM, McBride WH, Pajonk F (2006) The response of CD24(−/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst 98:1777–1785CrossRefGoogle Scholar
  42. 42.
    Galanzha EI, Kim JW, Zharov VP (2009) Nanotechnology-based molecular photoacoustic and photothermal flow cytometry platform for in vivo detection and killing of circulating cancer stem cells. J Biophotonics 2:725–735CrossRefGoogle Scholar
  43. 43.
    Galanzha EI, Shashkov EV, Kelly T, Kim JW, Yang L et al (2009) In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells. Nat Nanotechnol 4:855–860CrossRefGoogle Scholar
  44. 44.
    Kim JW, Galanzha EI, Shashkov EV, Moon HM, Zharov VP (2009) Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents. Nat Nanotechnol 4:688–694CrossRefGoogle Scholar
  45. 45.
    Hillner BE, Smith TJ (1991) Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer: a decision-analysis model. N Engl J Med 324(3):160–168CrossRefGoogle Scholar
  46. 46.
    Ning N, Pan Q, Zheng F, Teitz-Tennenbaum S, Egenti M, Yet J, Li M, Ginestier C, Wicha MS, Moyer JS, Prince MEP, Xu Y, Zhang X-L, Huang S, Chang AE, Li Q (2012) Cancer stem cell vaccination confers significant antitumor immunity. Cancer Res 72(7):1853. doi: 10.1158/0008-5472.CAN-11-1400 CrossRefGoogle Scholar
  47. 47.
    Xia X, Mai J, Wang R, Shen H (2015) Porous silicon microparticle potentiates anti-tumor immunity by enhancing cross-presentation and inducing type I interferon response. Cell Rep 11:957–966CrossRefGoogle Scholar
  48. 48.
    Biter B, Aird KAM, Garipov A, Li H, Amatangelo M, Zhang R et al (2015) Targeting EZH2 methyltransferase activity in ARID1A mutated cancer cells is synthetic lethal. Nat Med 21(3):231–238Google Scholar
  49. 49.
    Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbalý V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH (2012) NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer 48(14):2192–2202CrossRefGoogle Scholar
  50. 50.
    Stuckey DW et al (2015) Engineering toxin-resistant therapeutic stem cells to treat brain tumors. Stem Cells 33(2):589–600. doi: 10.1002/stem.1874 CrossRefGoogle Scholar
  51. 51.
    al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, Cooper J, Byhardt R, Davis L, Emami B (1997) Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol 15(1):277–284CrossRefGoogle Scholar
  52. 52.
    Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky R, Muss HB, Norton L (2003) Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21(8):1431–1439CrossRefGoogle Scholar
  53. 53.
    Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65(23):10946–10951CrossRefGoogle Scholar
  54. 54.
    Delaney G, Jacob S, Featherstone C, Barton M (2005) The role of radiotherapy in cancer treatment. Cancer 104(6):1129–1137CrossRefGoogle Scholar
  55. 55.
    Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H et al (1988) Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP Protocol R-011. J Nat Cancer I 80(1):21–29CrossRefGoogle Scholar
  56. 56.
    Gagliardi G, Lax I, Ottolenghi A, Rutqvist LE (1996) Long-term cardiac mortality after radiotherapy of breast cancer—application of the relative seriality model. Br J Radiol 69(825):839–846CrossRefGoogle Scholar

Copyright information

© The Author(s) 2015

Authors and Affiliations

  • Mirjana Pavlovic
    • 1
  • Bela Balint
    • 2
  1. 1.Department of Computer and Electrical Engineering and Computer ScienceFlorida Atlantic UniversityBoca RatonUSA
  2. 2.Military Medical Academy Institute for Hematology and TransfusiologyBelgradeSerbia

Personalised recommendations