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Cancer cell resistance mechanisms: a mini review

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Abstract

Cancer is a leading cause of death worldwide accounting to 13 % of all deaths. One of the main causes behind the failure of treatment is the development of various therapy resistance mechanisms by the cancer cells leading to the recurrence of the disease. This review sheds a light on some of the mechanisms developed by cancer cells to resist therapy as well as some of the structures involved such as the ABC members’ involvement in chemotherapy resistance and MET and survivin overexpression leading to radiotherapy resistance. Understanding those mechanisms will enable scientists to overcome resistance and possibly improve treatment and disease prognosis.

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References

  1. Garcia M, Jemal A. Global cancer facts and figures. Atlanta: American Cancer Society; 2007.

    Google Scholar 

  2. Baskar R, Lee KA, Yeo R, Yeoh K-W. Cancer and radiation therapy: current advances and future directions. Int J Med Sci. 2012;9(3):193–9. doi:10.7150/ijms.3635.

    Article  PubMed Central  PubMed  Google Scholar 

  3. American Cancer Society. Cancer facts and figures 2013. Atlanta: American Cancer Society; 2013. p 2013.

    Google Scholar 

  4. Dalkic E, Wang X, Wright N, Chan C. Cancer-drug associations: a complex system. PLoS One. 2010;5(4):e10031. doi:10.1371/journal.pone.0010031.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Hanahan D, Weinberg R. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. doi:10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  6. Bhosle J, Hall G. Principles of cancer treatment by chemotherapy. Surgery (Oxford). 2009;27(4):173–7.

    Article  Google Scholar 

  7. Borst P, Elferink R. Mammalian ABC transporters in health and disease. Annu Rev Biochem. 2002;71:537–92. doi:10.1146/annurev.biochem.71.102301.093055.

    Article  CAS  PubMed  Google Scholar 

  8. Dean M, Hamon Y, Chimini G. The human ATP-binding cassette (ABC) transporter superfamily. J of Lipid Res. 2001;11(7):1156–66.

    CAS  Google Scholar 

  9. Lubelski J, Konings W, Driessen A. Distribution and physiology of ABC-type transporters contributing to multidrug resistance in bacteria. Micro Mol Bio Rev. 2007;71(3):463–76. doi:10.1128/MMBR.00001-07.

    Article  CAS  Google Scholar 

  10. Chen J, Lu G, Davidson A, Qutocho F. A tweezers-like motion of the ATP-binding cassette dimer in an ABC transport cycle. Moll Cell. 2003;12(3):651–61.

    Article  CAS  Google Scholar 

  11. Sarkadi B, Homolya L, Szakacs G, Varadi A. Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system. Physiol Rev. 2006;86(4):1179–236. doi:10.1152/physrev.00037.2005.

    Article  CAS  PubMed  Google Scholar 

  12. Huff L, J-S LEE, Robey R, Fojo T. Characterization of gene rearrangements leading to activation of MDR-1. J Biol Chem. 2006;281(48):365019. doi:10.1074/jbc.M602998200.

    Article  Google Scholar 

  13. Stavrovskaya A, Stromskaya T. Transport proteins of the ABC family and multidrug resistance of tumor cells. Biochemistry. 2008;73(5):592–604. doi:10.1134/S0006297908050118.

    CAS  PubMed  Google Scholar 

  14. Davidson A, Elie D, Orelle C, Chen J. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol mol bio rev. 2008;72(2):317–64. doi:10.1128/MMBR.00031-07.

    Article  CAS  Google Scholar 

  15. Hipfner D, Deeley R, Cole S. Structural, mechanistic and clinical aspects of MRP1. Biochim Biophys Acta. 1999;1461(2):359–76. doi:10.1016/S0005-2736(99)00168-6.

    Article  CAS  PubMed  Google Scholar 

  16. Schwab M, Eichelbaum M, Fromm M. Genetic polymorphisms of the human MDR1 drug transporter. Annu Rev Pharmacol Toxicol. 2003;43:285–307. doi:10.1146/annurev.pharmtox.43.100901.140233.

    Article  CAS  PubMed  Google Scholar 

  17. González-Pons M, Szeto A, González-Méndez R, Serrano A. Identification and bioinformatic characterization of a multidrug resistance associated protein (ABCC) gene in Plasmodium berghei. Malar J. 2009;8:1. doi:10.1186/1475-2875-8-1.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Leslie E, Deeley R, Cole S. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharm. 2005;204(3):216–37. doi:10.1016/j.taap.2004.10.012.

    Article  CAS  Google Scholar 

  19. Yin J-Y, Huang Q, Yang Y, Zhang J-T, Zhong M-Z, Zhou H–H, et al. Characterization and analyses of multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphisms in Chinese population. Pharmacogenet Genomics. 2009;19(3):206–16. doi:10.1097/FPC.0b013e328323f680.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Kyle-Cezar F, Echevarria-Lima J, Goldenberg R, Rumjanek V. Expression of c-kit and Sca-1 and their relationship with multidrug resistance protein 1 in mouse bone marrow mononuclear cells. Immunology. 2007;121(1):122–8. doi:10.1111/j.1365-2567.2007.02547.x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Akan I, Akan S, Akca H, Savas B, Ozben T. Multidrug resistance-associated protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine sulfoximine. Cancer Cell Int. 2005;5:22. doi:10.1186/1475-2867-5-22.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Kasinathan R, Morgan W, Greenberg R. Schistosoma mansoni express higher levels of multidrug resistance-associated protein 1 (SmMRP1) in juvenile worms and in response to praziquantel. Mol Biochem Parasitol. 2010;173(1):25–31. doi:10.1016/j.molbiopara.2010.05.003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Mao Q, Unadkat J. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS Journal. 2005;7(1):E118–33. doi:10.1208/aapsj070112.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Marchan R, Hammond C, Ballatori N. Multidrug resistance-associated protein 1 as a major mediator of basal and apoptotic glutathione release. Biochim Biophys Acta. 2008;1778(10):2413–20. doi:10.1016/j.bbamem.2008.06.011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Mao Q, Unadkat J. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J. 2005;7(1):E118–33. doi:10.1208/aapsj070112.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Zhu M, Tong J, Xu Q, Nie F, Xu X, Xiao S, et al. Increased JNK1 signaling pathway is responsible for ABCG2-mediated multidrug resistance in human colon cancer. PLoS One. 2012;7(8):e41763. doi:10.1371/journal.pone.0041763.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Li X, Pan Y-Z, Seigel G, Hu Z-H, Huang M, Yu A-M. Breast cancer resistance protein BCRP/ABCG2 regulatory microRNAs (hsa-miR-328, -519c and -520 h) and their differential expression in stem-like ABCG2+ cancer cells. Biochem Pharmacol. 2011;81(6):783–92. doi:10.1016/j.bcp.2010.12.018.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Mo W, Zhang J-T. Human ABCG2: structure, function, and its role in multidrug resistance. Int J Biochem Mol Biol. 2012;3(1):1–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Begg A, Stewart F, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11:239–53. doi:10.1038/nrc3007.

    Article  CAS  PubMed  Google Scholar 

  30. Ghisolfi L, Keates A, Hu X, Lee D-k, Li C. Ionizing radiation induces stemness in cancer cells. PLoS One. 2012;7(8):e43628. doi:10.1371/journal.pone.0043628.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Suit H. Local control and patient survival. Int J of Rad Oncol Bio Phys. 1992;23(3):653–60. doi:10.1016/0360-3016(92)90025-D.

    Article  CAS  Google Scholar 

  32. Barcellos-Hoff M, Park C, Wright E. Radiation and the microenvironment—tumorigenesis and therapy. Nat Rev Cancer. 2005;5:867–75. doi:10.1038/nrc1735.

    Article  CAS  PubMed  Google Scholar 

  33. Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer. 2003;3(3):155–68. doi:10.1038/nrc1011.

    Article  CAS  PubMed  Google Scholar 

  34. Trusolino L, Comoglio P. Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer. 2002;2(4):289–300. doi:10.1038/nrc779.

    Article  CAS  PubMed  Google Scholar 

  35. De Bacco F, Luraghi P, Medico E, Reato G, Girolami F, Perera T, et al. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J Natl Cancer Inst. 2011;103(8):645–661. doi:10.1093/jnci/djr093.

    Article  PubMed  Google Scholar 

  36. Inanami O, Takahashi K, Kuwabara M. Attenuation of caspase-3-dependent apoptosis by Trolox post-treatment of X-irradiated MOLT-4 cells. Int J of Rad Bio. 1999;75(2):155–63. doi:10.1080/095530099140609.

    Article  CAS  Google Scholar 

  37. Ambrosini G, Adida C, Altieri D. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–21. doi:10.1038/nm0897-917.

    Article  CAS  PubMed  Google Scholar 

  38. Asanuma K, Moriai R, Yajima T, Yagihashi A, Yamada M, Kobayashi D, et al. Survivin as a radioresistance factor in pancreatic cancer. Jpn J Cancer Res. 2000;91(11):1204–9. doi:10.1111/j.1349-7006.2000.tb00906.x.

    Article  CAS  PubMed  Google Scholar 

  39. Dillman R, Fogel GB, Cornforth AN, Selvan SR, Schiltz PM, DePriest C. Features associated with survival in metastatic melanoma patients treated with patient-specific dendritic cell vaccines. Cancer Biother Radiopharm. 2011;26(4):407–15. doi:10.1089/cbr.2011.0973.

    Article  CAS  PubMed  Google Scholar 

  40. Dunn G, Old L, Schreiber R. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137–48. doi:10.1016/j.immuni.2004.07.017.

    Article  CAS  PubMed  Google Scholar 

  41. Schreiber R, Old L, Smyth M. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70. doi:10.1126/science.1203486.

    Article  CAS  PubMed  Google Scholar 

  42. Marincola F, Jaffee E, Hicklin D, Ferrone S. Escape of human solid tumors from T–cell recognition: molecular mechanisms and functional significance. Adv Immuno. 2000;74:181–273. doi:10.1016/S0065-2776(08)60911-6.

    Article  CAS  Google Scholar 

  43. Ribas A, Butterfield L, Glaspy J, Economou J. Current developments in cancer vaccines and cellular immunotherapy. J of Clin Oncol. 2003;21(12):2415–32. doi:10.1200/JCO.2003.06.041.

    Article  CAS  Google Scholar 

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Al-Dimassi, S., Abou-Antoun, T. & El-Sibai, M. Cancer cell resistance mechanisms: a mini review. Clin Transl Oncol 16, 511–516 (2014). https://doi.org/10.1007/s12094-014-1162-1

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  • DOI: https://doi.org/10.1007/s12094-014-1162-1

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