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Immunotoxins, Resistance and Cancer Stem Cells: Future Perspective

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Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 6)

Abstract

Cancer relapse or recurrence has been the greatest challenge in the treatment of this life threatening disease, which occurs due to resistance of cancer cells to drug or radiation therapy. Most often this resistance is developed during treatment, which makes it even more complicated, leading to the failure of chemo or radiation therapy in the majority of cases. To circumvent these problems associated with conventional therapies, newer strategies were adopted like targeted therapy using monoclonal antibodies, immunotoxins and antibody-drug conjugates. However, targeted therapy also showed failure in many in vitro and in vivo studies that was again attributed to the emergence of resistant cells. Here, we discuss the various factors and cellular mechanisms responsible for resistance against conventional therapies and targeted approaches like recombinant immunotoxins. Cancer stem cells (CSC’s) were identified as the major reason for resistance and their role in cancer relapse has been proved convincingly in recent studies. Hence, resistance mechanisms involved in CSC’s have been elaborated. We also summarize the strategies being adopted currently to overcome resistance and different means of targeting resistant cancer stem cells that could be used in the future.

Keywords

Immunotoxins Cancer resistance Cancer stem cells Drug efflux Survival pathway Chemotherapy 

Abbreviations

ABC

ATP-Binding Cassette

AML

Acute myeloid leukemia

BCRP

Breast cancer resistance protein

BTK

Bruton tyrosine kinase

CSC

Cancer stem cells

DAMP

Damage-associated molecular patterns

DT

Diphtheria toxin

EMT

Epithelial Mesenchymal transition

GCS

GlcCer synthase

GO

Gemtuzumab ozogamicin

GSIs

Gamma-secretase inhibitors

HIF

Hypoxia inducible factor

IT

Immunotoxin

MCL

Mantle cell lymphoma

MDR

Multi Drug Resistance

MRP1

Multidrug resistance protein 1

OV

Oncolytic viruses

P-gp

P-glycoprotein

SCLC

Small Cell Lung Cancer

SCNP

Single cell network profiling

T-ALL

T cell acute lymphoblastic leukemia

TMM

Telomere maintenance mechanisms

Tnfaip3

Tumor necrosis factor alpha induced protein 3

TRAIL

TNF-related apoptosis-inducing ligand

VEGF

Vascular endothelial growth factor

Notes

Acknowledgement

This research was supported in part by Department of Science and Technology and Department of Biotechnology, Government of India.

References

  1. 1.
    Harris AL, Hochhauser D Mechanisms of multidrug resistance in cancer treatment. Acta Oncol. 1992;31(2):205–13.PubMedCrossRefGoogle Scholar
  2. 2.
    Jamroziak K, Robak T. Pharmacogenomics of MDR1/ABCB1 gene: the influence on risk and clinical outcome of haematological malignancies. Hematology. 2004;9(2):91–105.PubMedCrossRefGoogle Scholar
  3. 3.
    Leighton JC Jr, Goldstein LJ. P-glycoprotein in adult solid tumors. Expression and prognostic significance. Hematol Oncol Clin North Am. 1995;9(2):251–73.PubMedGoogle Scholar
  4. 4.
    Hanahan D, Weinberg RA. Hallmarks of Cancer: the next generation. Cell. 2011;144(5):646–74.PubMedCrossRefGoogle Scholar
  5. 5.
    Giaccia AJ, Schipani E. Role of carcinoma-associated fibroblasts and hypoxia in tumor progression. Curr Top Microbiol Immunol. 2010;345:31–45.PubMedGoogle Scholar
  6. 6.
    da Silva CG, Minussi DC, Ferran C, Bredel M. A20 expressing tumors and anticancer drug resistance. Adv Exp Med Biol. 2014;809:65–81.PubMedGoogle Scholar
  7. 7.
    Pujari R, Hunte R, Khan WN, Shembade N. A20-mediated negative regulation of canonical NF-κB signaling pathway. Immunol Res. 2013;57(1–3):166–71.PubMedCrossRefGoogle Scholar
  8. 8.
    Perez-Galan P, Dreyling M, Wiestner A. Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era. Blood. 2011;117:26–38.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Liang DC, Shih LY, Hung IJ, Yang CP, Chen SH, Jaing TH, Liu HC, Wang LY, Chang WH. FLT3-TKD mutation in childhood acute myeloid leukemia. Leukemia. 2003;17(5):883–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Piovan E, Yu J, Tosello V, Herranz D, Ambesi-Impiombato A, Silva AC D, Sanchez-Martin M, Perez-Garcia A, Rigo I, Castillo M, Indraccolo S, Cross JR, de Stanchina E, Paietta E, Racevskis J, Rowe JM, Tallman MS, Basso G, Meijerink JP, Cordon-Cardo C, Califano A, Ferrando AA. Direct reversal of glucocorticoid resistance by AKT inhibition in acute lymphoblastic leukemia. Cancer Cell. 2013;24(6):766–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Small S. Ibrutinib approved for the treatment of mantle cell lymphoma. Clin Adv Hematol Oncol. 2013;11(12):808.Google Scholar
  12. 12.
    Wilson WH, Sorbara L, Figg WD, Mont EK, Sausville E, Warren KE, Balis FM, Bauer K, Raffeld M, Senderowicz AM, Monks A. Modulation of clinical drug resistance in a B cell lymphoma patient by the protein kinase inhibitor 7-hydroxystaurosporine: presentation of a novel therapeutic paradigm. Clin Cancer Res. 2000;6(2):415–21.PubMedGoogle Scholar
  13. 13.
    Chiron D, Liberto M D, Martin P, Huang X, Sharman J, Blecua P, Mathew S, Vijay P, Eng K, Ali S, Johnson A, Chang B, Ely S, Elemento O, Mason CE, Leonard JP, Chen-Kiang S. Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov. 2014;4(9):1022–35.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Williams AB, Nguyen B, Li L, Brown P, Levis M, Leahy D, Small D. Mutations of FLT3/ITD confer resistance to multiple tyrosine kinase inhibitors. Leukemia. 2013;27(1):48–55.PubMedCrossRefGoogle Scholar
  15. 15.
    Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986;47(3):381–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Coley HM. Overcoming multidrug resistance in cancer: clinical studies of p-glycoprotein inhibitors. Methods Mol Biol. 2010;596:341–58.PubMedGoogle Scholar
  17. 17.
    Pietro A D, Dayan G, Conseil G, Steinfels E, Krell T, Trompier D, Baubichon-Cortay H, Jault J. P-glycoprotein-mediated resistance to chemotherapy in cancer cells: using recombinant cytosolic domains to establish structure-function relationships. Braz J Med Biol Res. 1999;32(8):925–39.PubMedCrossRefGoogle Scholar
  18. 18.
    Sarkadi B, Ozvegy-Laczka C, Nemet K, Varadi A. ABCG2- a transporter for all seasons. FEBS Lett. 2004;567:116–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Yasuda H. Solid tumor physiology and hypoxia-induced chemo/radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer. Nitric Oxide. 2008;19(2):205–16.PubMedCrossRefGoogle Scholar
  20. 20.
    Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26(2):225–39.PubMedCrossRefGoogle Scholar
  21. 21.
    Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem. 1994;269(38):23757–63.PubMedGoogle Scholar
  22. 22.
    Walter RB, Raden BW, Kamikura DM, Cooper JA, Bernstein ID. Influence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity. Blood. 2005;105:1295–302.PubMedCrossRefGoogle Scholar
  23. 23.
    Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res. 2014;16(2):209.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Haag P, Viktorsson K, Lindberg ML, Kanter L, Lewensohn R, Stenke L. Deficient activation of Bak and Bax confers resistance to gemtuzumab ozogamicin-induced apoptotic cell death in AML. Exp Hematol. 2009;37(6):755–66.PubMedCrossRefGoogle Scholar
  25. 25.
    Linenberger ML. CD33-directed therapy with gemtuzumab ozogamicin in acute myeloid leukemia: progress in understanding cytotoxicity and potential mechanisms of drug resistance. Leukemia. 2005;19(2):176–82.PubMedCrossRefGoogle Scholar
  26. 26.
    Traini R, Ben-Josef G, Pastrana DV, Moskatel E, Sharma AK, Antignani A, Fitzgerald DJ. ABT-737 overcomes resistance to immunotoxin-mediated exotoxin-based proteins to the cell cytosol apoptosis and enhances the delivery of pseudomonas. Mol Cancer Ther. 2010;9(7):2007–15.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Cianfriglia M, Mallano A, Ascione A, Dupuis ML. Multidrug transporter proteins and cellular factors involved in free and mAb linked calicheamicin-Á1 (gentuzumab ozogamicin, GO) resistance and in the selection of GO resistant variants of the HL60 AML cell line. Int J Oncol. 2010;36(6):1513–20.PubMedCrossRefGoogle Scholar
  28. 28.
    Walter RB, Raden BW, Hong TC, Flowers DA, Bernstein ID, Linenberger ML. Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells. Blood. 2003;102(4):1466–73.PubMedCrossRefGoogle Scholar
  29. 29.
    McGrath MS, Rosenblum MG, Philips MR, Scheinberg DA. Immunotoxin resistance in multidrug resistant cells. Cancer Res. 2003;63(1):72–9.PubMedGoogle Scholar
  30. 30.
    Weldon JE, Xiang L, Chertov O, Margulies I, Kreitman RJ, FitzGerald DJ, Pastan I. A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity. Blood. 2009;113(16):3792–800.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Hazes B, Read RJ. Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. BioChemistry. 1997;36(37):11051–4.PubMedCrossRefGoogle Scholar
  32. 32.
    Engert A, Brown A, Thorpe P. Resistance of myeloid leukaemia cell lines to ricin A-chain immunotoxins. Leuk Res. 1991;15(11):1079–86.PubMedCrossRefGoogle Scholar
  33. 33.
    Hu X, Wei H, Xiang L, Chertov O, Wayne AS, Bera TK, Pastan I. Methylation of the DPH1 promoter causes immunotoxin resistance in acute lymphoblastic leukemia cell line KOPN-8. Leuk Res. 2013;37(11):1551–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Wei H, Xiang L, Wayne AS, Chertov O, FitzGerald DJ, Bera TK, Pastan I. Immunotoxin resistance via reversible methylation of the DPH4 promoter is a unique survival strategy. Proc Natl Acad Sci U S A. 2012;109(18):6898–903.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Wei H, Bera TK, Wayne AS, Xiang L, Colantonio S, Chertov O, Pastan IA. Modified form of diphthamide causes immunotoxin resistance in a lymphoma cell line with a deletion of the WDR85 gene. J Biol Chem. 2013;288(17):12305–12.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Rosen DB, Harrington KH, Cordeiro JA, Leung LY, Putta S, Lacayo N, Laszlo GS, Gudgeon CJ, Hogge DE, Hawtin RE, Cesano A, Walter RB. AKT signalling as a novel factor associated with in vitro resistance of human AML to gemtuzumab ozogamicin. PLoS ONE. 2013;8(1):e53518.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Ding K, Banerjee A, Tan S, Zhao J, Zhuang Q, Li R, Qian P, Liu S, Wu ZS, Lobie PE, Zhu T. Artemin, a member of the glial cell line-derived neurotrophic factor family of ligands, is HER2-regulated and mediates acquired trastuzumab resistance by promoting cancer stem cell-like behavior in mammary carcinoma cells. J Biol Chem. 2014;289(23):16057–71.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Cojoc M, Mäbert K, Muders MH, Dubrovska A. A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms. Semin Cancer Biol. 2014;31:16–27.Google Scholar
  39. 39.
    Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5(4):275–84.PubMedCrossRefGoogle Scholar
  40. 40.
    Vinogradov S, Wei X Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine (Lond). 2012;7(4):597–615.CrossRefGoogle Scholar
  41. 41.
    Hombach-Klonisch S, Natarajan S, Thanasupawat T, Medapati M, Pathak A, Ghavami S, Klonisch T. Mechanisms of therapeutic resistance in cancer (stem) cells with emphasis on thyroid cancer cells. Front Endocrinol (Lausanne). 2014;5:37.Google Scholar
  42. 42.
    Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong KK, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010;141(1):69–80.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Borst P. Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what? Open Biol. 2012;2(5):120066.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Folini M Editorial: targeting telomere maintenance mechanisms in cancer therapy. Curr Pharm Des. 2014;20(41):6359–60.PubMedCrossRefGoogle Scholar
  45. 45.
    Reddel RR. Telomere maintenance mechanisms in human cancer: clinical implications. Curr Pharm Des. 2014;20(41):6361–74.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Feijoo P, Dominguez D, Tusell L, Genesca A. Telomere-dependent genomic integrity: evolution of the fusion-bridge-breakage cycle concept. Curr Pharm Des. 2014;20(41):6375–85.PubMedCrossRefGoogle Scholar
  47. 47.
    Krause DS, Van Etten RA. Right on target: eradicating leukemic stem cells. Trends Mol Med. 2007;13(11):470–81.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Essers MAG, Trumpp A. Targeting leukemic stem cells by breaking their dormancy. Mol Oncol. 2010;4:443 -450.Google Scholar
  49. 49.
    Moore J, Seiter K, Kolitz J, Stock W, Giles F, Kalaycio M, Zenk D, Marcucci G. A phase II study of Bcl-2 antisense (oblimersen sodium) combined with gemtuzumab ozogamicin in older patients with acute myeloid leukemia in first relapse. Leuk Res. 2006;30:777–83.PubMedCrossRefGoogle Scholar
  50. 50.
    Grodzovski I, Lichtenstein M, Galski H, Lorberboum-Galski H. IL-2-granzyme A chimeric protein overcomes multidrug resistance (MDR) through a caspase 3-independent apoptotic pathway. Int J Cancer. 2011;128(8):1966–80.PubMedCrossRefGoogle Scholar
  51. 51.
    Mattoo AR, FitzGerald DJ. Combination treatments with ABT-263 and an immunotoxin produce synergistic killing of ABT-263-resistant small cell lung cancer cell lines. Int J Cancer. 2013;132(4):978–87.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Secchiero P, Vaccarezza M, Gonelli A, Zauli G. TNF-related apoptosis-inducing ligand (TRAIL): a potential candidate for combined treatment of hematological malignancies. Curr Pharm Des. 2004;10(29):3673–81.PubMedCrossRefGoogle Scholar
  53. 53.
    Cenni V, Maraldi NM, Ruggeri A, Secchiero P, Del Coco R, De Pol A, Cocco L, Marmiroli S. Sensitization of multidrug resistant human ostesarcoma cells to Apo2 Ligand/TRAIL-induced apoptosis by inhibition of the Akt/PKB kinase. Int J Oncol. 2004;25(6):1599–608.PubMedGoogle Scholar
  54. 54.
    Du X, Xiang L, Mackall C, Pastan I. Killing of resistant cancer cells with low Bak by a combination of an antimesothelin immunotoxin and a TRAIL receptor 2 agonist antibody. Clin Cancer Res. 2011;17:5926–34.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Yamanaka K, Rocchi P, Miyake H, Fazli LA, So A, Zangemeister-Wittke U, Gleave ME. Induction of apoptosis and enhancement of chemosensitivity in human prostate cancer LNCaP cells using bispecific antisense oligonucleotide targeting Bcl-2 and Bcl-xL genes. BJU Int. 2006;97:1300–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Indran IR, Tufo G, Pervaiz S, Brenner C. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim Biophys Acta. 2011;1807:735–45.PubMedCrossRefGoogle Scholar
  57. 57.
    Hamada H, Tsuruo T Functional role for the 170- to 180-kDa glycoprotein specific to drug-resistant tumor cells as revealed by monoclonal antibodies. Proc Natl Acad Sci U S A. 1986;83(20):7785–9.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    FitzGerald DJ, Willingham MC, Cardarelli CO, Hamada H, Tsuruo T, Gottesman MM, Pastan I. A monoclonal antibody-Pseudomonas toxin conjugate that specifically kills multidrug-resistant cells. Proc Natl Acad Sci U S A. 1987;84:4288–92.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Mickisch GH, Pai LH, Gottesman MM, Pastan I. Monoclonal antibody MRK16 reverses the multidrug resistance of multi-drug resistant transgenic mice. Cancer Res. 1992;52(16):4427–32.PubMedGoogle Scholar
  60. 60.
    Dinota A, Tazzari PL, Michieli M, Visani G, Gobbi, M, Bontadini A, Tassi C, Fanin R, Damiani D, Grandi M, Pileri S, Bolognesi A, Stirpe F, Baccarani M, Tsuruo T, Tura S. In vitro bone marrow purging of multidrug-resistant cells with a mouse monoclonal antibody directed against Mr 170,000 glycoprotein and Saporin-conjugated anti-mouse antibody. Cancer Res. 1990;50:4291–4.PubMedGoogle Scholar
  61. 61.
    Niv R, Assaraf YG, Segal D, Pirak E, Reiter Y. Targeting multidrug resistant tumor cells with a recombinant single-chain FV fragment directed to P-glycoprotein. Int J Cancer. 2001;94(6):864–72.PubMedCrossRefGoogle Scholar
  62. 62.
    St’astný M, Strohalm J, Plocová D, Ulbrich K, Ríhová B. A possibility to overcome P-glycoprotein (PGP)-mediated multidrug resistance by antibody-targeted drugs conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier. Eur J Cancer. 1999;35(3):459–66.CrossRefGoogle Scholar
  63. 63.
    Takeshita A. Efficacy and resistance of gemtuzumabozogamicin for acute myeloid leukemia. Int J Hematol. 2013;97(6):703–16.PubMedCrossRefGoogle Scholar
  64. 64.
    Matsui H, Takeshita A, Naito K, Shinjo K, Shigeno K, Maekawa M, Yamakawa Y, Tanimoto M, Kobayashi M, Ohnishi K, Ohno R. Reduced effect of gemtuzumabozogamicin (CMA-676) on P-glycoprotein and/or CD34-positive leukemia cells and its restoration by multidrug resistance modifiers. Leukemia. 2002;16(5):813–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Tortorella LL, Pipalia NH, Mukherjee S, Pastan I, Fitzgerald D, Maxfield FR. Efficiency of immunotoxin cytotoxicity is modulated by the intracellular itinerary. PLoS ONE. 2012;7:e47320.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Alewine C, Xiang L, Yamori T, Niederfellner G, Bosslet K, Pastan I. Efficacy of RG7787, a next generation mesothelin-targeted immunotoxin, against triple-negative breast and gastric cancers. Mol Cancer Ther. 2014;13(11):2653–61.Google Scholar
  67. 67.
    Folini M Editorial: targeting telomere maintenance mechanisms in cancer therapy. Curr Pharm Des. 2014;20(41):6359–60.PubMedCrossRefGoogle Scholar
  68. 68.
    Santambrogio F, Gandellini P, Cimino-Reale G, Zaffaroni N, Folini M. MicroRNA-dependent regulation of telomere maintenance mechanisms: a field as much unexplored as potentially promising. Curr Pharm Des. 2014;20(41):6404–21.PubMedCrossRefGoogle Scholar
  69. 69.
    Crees Z, Girard J, Rios Z, Botting GM, Harrington K, Shearrow C, Wojdyla L, Stone AL, Uppada SB, Devito JT, Puri N. Oligonucleotides and G-quadruplex stabilizers: targeting telomeres and telomerase in cancer therapy. Curr Pharm Des. 2014;20(41):6422–37.PubMedCrossRefGoogle Scholar
  70. 70.
    Romaniuk A, Kopczy_ski P, Ksi_ek K, Rubi B. Telomerase as a target for anticancer therapies. Curr Pharm Des. 2014;20(41):6438–51.PubMedCrossRefGoogle Scholar
  71. 71.
    Uziel O, Lahav M. Conventional anticancer therapeutics and telomere maintenance mechanisms. Curr Pharm Des. 2014;20(41):6452–65.PubMedCrossRefGoogle Scholar
  72. 72.
    Jabbour E, Ottmann OG, Deininger M, Hochhaus A. Targeting the phosphoinositide 3-kinase pathway in hematologic malignancies. Haematologica. 2014;99(1):7–18.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Post J, Vooijs WC, Bast BJ, De Gast GC. Efficacy of an anti-CD138 immunotoxin and doxorubicin on drug-resistant and drug-sensitive myeloma cells. Int J Cancer. 1999;83(4):571–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Liu C, Lambert JM, Teicher BA, Blättler WA, O’Connor R. Cure of multidrug-resistant human B-Cell lymphoma xenografts by combinations of anti-B4-blocked ricin and chemotherapeutic drugs. Blood. 1996;87(9):3892–8.PubMedGoogle Scholar
  75. 75.
    Rosenblum MG, Cheung L, Kim SK, Mujoo K, Donato NJ, Murray JL. Cellular resistance to the antimelanoma immunotoxin ZME-gelonin and strategies to target resistant cells. Cancer Immunol Immunother. 1996;42(2):115–21.PubMedCrossRefGoogle Scholar
  76. 76.
    Wagstaff KM, Jans DA. Protein transduction: cell penetrating peptides and their therapeutic applications. Curr Med Chem. 2006;13(12):1371–87.PubMedCrossRefGoogle Scholar
  77. 77.
    Liu J, Zhao Y, Guo Q, Wang Z, Wang H, Yang Y, Huang Y. TAT-modified nanosilver for combating multidrug-resistant cancer. Biomaterials. 2012;33(26):6155–61.PubMedCrossRefGoogle Scholar
  78. 78.
    Kirtane AR, Kalscheuer SM, Panyam J. Exploiting nanotechnology to overcome tumor drug resistance: challenges and opportunities. Adv Drug Deliv Rev. 2013;65(13–14):1731–47.PubMedCrossRefGoogle Scholar
  79. 79.
    Beljanski V, Hiscott J. The use of oncolytic viruses to overcome lung cancer drug resistance. Curr Opin Virol. 2012;2(5):629–35.PubMedCrossRefGoogle Scholar
  80. 80.
    Pavelic J. Editorial: combined cancer therapy. Curr Pharm Des. 2014;20(42):6511–2.PubMedCrossRefGoogle Scholar
  81. 81.
    Han L, Shi S, Gong T, Zhang Z, Sun X. Cancer stem cells: therapeutic implications and perspectives in cancer therapy. Acta Pharmaceutica Sinica B. 2013;3(2):65–75.CrossRefGoogle Scholar
  82. 82.
    Ischenko I, Seeliger H, Schaffer M, Jauch KW, Bruns CJ. Cancer stem cells: how can we target them? Curr Med Chem. 2008;15:3171–84.PubMedCrossRefGoogle Scholar
  83. 83.
    Sun S, Liu S, Duan SZ, Zhang L, Zhou H, Hu Y, Zhou X, Shi C, Zhou R, Zhang Z. Targeting the c-Met/FZD8 signaling axis eliminates patient-derived cancer stem-like cells in head and neck squamous carcinomas. Cancer Res. 2014;74(24):7546–59Google Scholar
  84. 84.
    Huang H, Hu M, Li P, Lu C, Li M. Mir-152 inhibits cell proliferation and colony formation of CD133 + liver cancer stem cells by targeting KIT. Tumour Biol. 2014;36(2):921–8.Google Scholar
  85. 85.
    Bao B, Azmi AS, Ali S, Zaiem F, Sarkar FH. Metformin may function as anti-cancer agent via targeting cancer stem cells: the potential biological significance of tumor associated miRNAs in breast and pancreatic cancers. Ann Transl Med. 2014;2(6):59.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Bao S, Wu Q, Li Z, Sathornsumetee S, Wang H, McLendon RE, Hjelmeland AB, Rich JN. Targeting cancer stem cells through L1CAM suppresses glioma growth. Cancer Res. 2008;68(15):6043–8.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Hogge DE, Feuring-Buske M, Gerhard B, Frankel AE. The efficacy of diphtheria-growth factor fusion proteins is enhanced by co-administration of cytosine arabinoside in an immunodeficient mouse model of human acute myeloid leukemia. Leuk Res. 2004;28(11):1221–6.PubMedCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Stem Cell and Molecular Biology laboratory, Department of BiotechnologyIndian Institute of Technology MadrasChennaiIndia

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