| Peer-Reviewed

General Mechanisms of Resistance to Pharmacological Therapy Applied to Tumor Cells

Received: 27 July 2018     Accepted: 9 August 2018     Published: 6 September 2018
Views:       Downloads:
Abstract

The management of cancer involves procedures, which include surgery, radiotherapy and chemotherapy, whose are aimed at destroying tumor cells and preserving healthy tissues. Development of drug resistance is one of problems during the treatment of local and/or disseminated disease, also is one of the biggest problems in relapses of cancer. A plethora of cytotoxic drugs that selectively, but not exclusively, target actively proliferating cells include such diverse groups as DNA alkylating agents, antimetabolites, intercalating agents and mitotic inhibitors. Resistance constitutes a lack of response to drug-induced tumor growth inhibition. This article discusses the various mechanisms of acquired drug resistance that have been reported in the context of cancer drug therapies. The drug resistance may be inherent in a subpopulation of heterogeneous cancer cells or be acquired as a cellular response to drug exposure. Also, different mechanisms have been proposed that could explain tumor refractoriness due to resistance to anti-tumor drugs, some of them are: intrinsic resistance due to their genetic characteristics, acquisition of resistance mechanisms after exposure to a drug, mechanisms that alter transport of the drug. drug through the plasma membrane, DNA repair, alterations in target molecules, difficulty of the drug to access the target cells and growth factors. The knowledge of these mechanisms of resistance, could serve as a therapeutic strategy to control or delay the progression of the disease and therefore improve the quality of life of the patient.

Published in Cancer Research Journal (Volume 6, Issue 3)
DOI 10.11648/j.crj.20180603.15
Page(s) 101-105
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2018. Published by Science Publishing Group

Keywords

Cancer, Chemotherapy, Pharmacological Resistance, Tumor Cell

References
[1] Fernández-Lázaro D. Análisis pre-clínico comparativo de la eficacia, mecanismo de acción y mecanismos de resistencia de dos fármacos inmunomoduladores (IMIDS), lenalidomida y pomalidomida, en mieloma múltiple. [Doctoral]. Salamanca: Salamanca; 2011.
[2] Fodale V, Pierobon M, Liotta L, Petricoin E. Mechanism of cell adaptation: when and how do cancer cells develop chemoresistance? Cancer J. 2011; 17(2):89-95.
[3] Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001; 11(7):1156-66.
[4] Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci. 2000; 11(4):265-83.
[5] Wang XJ, Zhang DL, Fu C, Wei BZ, Li GJ. MiR-183 modulates multi-drug resistance in hepatocellular cancer (HCC) cells via miR-183-IDH2/SOCS6-HIF-1alpha feedback loop. Eur Rev Med Pharmacol Sci. 2016; 20(10):2020-7.
[6] Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976; 455(1):152-62.
[7] Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, 3rd, Hurov KE, Luo J, et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007; 316(5828):1160-6.
[8] Kartner N, Riordan JR, Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science (New York, NY. 1983; 221(4617):1285-8.
[9] Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, et al. 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.
[10] Szakacs G, Annereau JP, Lababidi S, Shankavaram U, Arciello A, Bussey KJ, et al. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer cell. 2004; 6(2):129-37.
[11] Marie JP, Zittoun R, Sikic BI. Multidrug resistance (mdr1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity. Blood. 1991; 78(3):586-92.
[12] Fischer S, Pietsch M, Schirmer K, Luckenbach T. Identification of multi-drug resistance associated proteins MRP1 (ABCC1) and MRP3 (ABCC3) from rainbow trout (Oncorhynchus mykiss). Mar Environ Res. 2010; 69 Suppl:S7-S10.
[13] Ross DD, Yang W, Abruzzo LV, Dalton WS, Schneider E, Lage H, et al. Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. Journal of the National Cancer Institute. 1999; 91(5):429-33.
[14] Benderra Z, Faussat AM, Sayada L, Perrot JY, Chaoui D, Marie JP, et al. Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias. Clin Cancer Res. 2004; 10(23):7896-902.
[15] Steinbach D, Sell W, Voigt A, Hermann J, Zintl F, Sauerbrey A. BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia. Leukemia. 2002; 16(8):1443-7.
[16] Damiani D, Tiribelli M, Calistri E, Geromin A, Chiarvesio A, Michelutti A, et al. The prognostic value of P-glycoprotein (ABCB) and breast cancer resistance protein (ABCG2) in adults with de novo acute myeloid leukemia with normal karyotype. Haematologica. 2006;91(6):825-8.
[17] Benderra Z, Faussat AM, Sayada L, Perrot JY, Tang R, Chaoui D, et al. MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia. Clin Cancer Res. 2005; 11(21):7764-72.
[18] Sánchez-Suárez P, Benítez-Bribiesca L. Procesos biomoleculares de la Resistencia a drogas. Cancerolgía 2006; 1:18-199.
[19] Ansari M, Krajinovic M. Pharmacogenomics of acute leukemia. Pharmacogenomics. 2007; 8(7):817-34.
[20] Bolufer P, Collado M, Barragan E, Cervera J, Calasanz MJ, Colomer D, et al. The potential effect of gender in combination with common genetic polymorphisms of drug-metabolizing enzymes on the risk of developing acute leukemia. Haematologica. 2007; 92(3):308-14.
[21] McCubrey JA, Abrams SL, Ligresti G, Misaghian N, Wong EW, Steelman LS, et al. Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance. Leukemia. 2008; 22(11):2080-90.
[22] McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F, Bertrand FE, et al. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzyme Regul. 2006; 46:249-79.
[23] Steelman LS, Abrams SL, Whelan J, Bertrand FE, Ludwig DE, Basecke J, et al. Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia. Leukemia. 2008; 22(4):686-707.
[24] Galmarini CM, Kamath K, Vanier-Viornery A, Hervieu V, Peiller E, Falette N, et al. Drug resistance associated with loss of p53 involves extensive alterations in microtubule composition and dynamics. Br J Cancer. 2003; 88(11):1793-9.
[25] Chaudhry P, Asselin E. Resistance to chemotherapy and hormone therapy in endometrial cancer. Endocr Relat Cancer. 2009; 16(2):363-80.
[26] Das-Gupta EP, Seedhouse CH, Russell NH. DNA repair mechanisms and acute myeloblastic leukemia. Hematological oncology. 2000; 18(3):99-110.
[27] Henriquez OC, Baez SM, Von Oetinger A, Canas JR, Ramirez CR. Autonomic control of heart rate after exercise in trained wrestlers. Biol Sport. 2013; 30(2):111-5.
[28] Furuta T, Ueda T, Aune G, Sarasin A, Kraemer KH, Pommier Y. Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells. Cancer Res. 2002; 62(17):4899-902.
Cite This Article
  • APA Style

    Fernández-Lázaro Diego, Fernández-Lázaro César Ignacio. (2018). General Mechanisms of Resistance to Pharmacological Therapy Applied to Tumor Cells. Cancer Research Journal, 6(3), 101-105. https://doi.org/10.11648/j.crj.20180603.15

    Copy | Download

    ACS Style

    Fernández-Lázaro Diego; Fernández-Lázaro César Ignacio. General Mechanisms of Resistance to Pharmacological Therapy Applied to Tumor Cells. Cancer Res. J. 2018, 6(3), 101-105. doi: 10.11648/j.crj.20180603.15

    Copy | Download

    AMA Style

    Fernández-Lázaro Diego, Fernández-Lázaro César Ignacio. General Mechanisms of Resistance to Pharmacological Therapy Applied to Tumor Cells. Cancer Res J. 2018;6(3):101-105. doi: 10.11648/j.crj.20180603.15

    Copy | Download

  • @article{10.11648/j.crj.20180603.15,
      author = {Fernández-Lázaro Diego and Fernández-Lázaro César Ignacio},
      title = {General Mechanisms of Resistance to Pharmacological Therapy Applied to Tumor Cells},
      journal = {Cancer Research Journal},
      volume = {6},
      number = {3},
      pages = {101-105},
      doi = {10.11648/j.crj.20180603.15},
      url = {https://doi.org/10.11648/j.crj.20180603.15},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20180603.15},
      abstract = {The management of cancer involves procedures, which include surgery, radiotherapy and chemotherapy, whose are aimed at destroying tumor cells and preserving healthy tissues. Development of drug resistance is one of problems during the treatment of local and/or disseminated disease, also is one of the biggest problems in relapses of cancer. A plethora of cytotoxic drugs that selectively, but not exclusively, target actively proliferating cells include such diverse groups as DNA alkylating agents, antimetabolites, intercalating agents and mitotic inhibitors. Resistance constitutes a lack of response to drug-induced tumor growth inhibition. This article discusses the various mechanisms of acquired drug resistance that have been reported in the context of cancer drug therapies. The drug resistance may be inherent in a subpopulation of heterogeneous cancer cells or be acquired as a cellular response to drug exposure. Also, different mechanisms have been proposed that could explain tumor refractoriness due to resistance to anti-tumor drugs, some of them are: intrinsic resistance due to their genetic characteristics, acquisition of resistance mechanisms after exposure to a drug, mechanisms that alter transport of the drug. drug through the plasma membrane, DNA repair, alterations in target molecules, difficulty of the drug to access the target cells and growth factors. The knowledge of these mechanisms of resistance, could serve as a therapeutic strategy to control or delay the progression of the disease and therefore improve the quality of life of the patient.},
     year = {2018}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - General Mechanisms of Resistance to Pharmacological Therapy Applied to Tumor Cells
    AU  - Fernández-Lázaro Diego
    AU  - Fernández-Lázaro César Ignacio
    Y1  - 2018/09/06
    PY  - 2018
    N1  - https://doi.org/10.11648/j.crj.20180603.15
    DO  - 10.11648/j.crj.20180603.15
    T2  - Cancer Research Journal
    JF  - Cancer Research Journal
    JO  - Cancer Research Journal
    SP  - 101
    EP  - 105
    PB  - Science Publishing Group
    SN  - 2330-8214
    UR  - https://doi.org/10.11648/j.crj.20180603.15
    AB  - The management of cancer involves procedures, which include surgery, radiotherapy and chemotherapy, whose are aimed at destroying tumor cells and preserving healthy tissues. Development of drug resistance is one of problems during the treatment of local and/or disseminated disease, also is one of the biggest problems in relapses of cancer. A plethora of cytotoxic drugs that selectively, but not exclusively, target actively proliferating cells include such diverse groups as DNA alkylating agents, antimetabolites, intercalating agents and mitotic inhibitors. Resistance constitutes a lack of response to drug-induced tumor growth inhibition. This article discusses the various mechanisms of acquired drug resistance that have been reported in the context of cancer drug therapies. The drug resistance may be inherent in a subpopulation of heterogeneous cancer cells or be acquired as a cellular response to drug exposure. Also, different mechanisms have been proposed that could explain tumor refractoriness due to resistance to anti-tumor drugs, some of them are: intrinsic resistance due to their genetic characteristics, acquisition of resistance mechanisms after exposure to a drug, mechanisms that alter transport of the drug. drug through the plasma membrane, DNA repair, alterations in target molecules, difficulty of the drug to access the target cells and growth factors. The knowledge of these mechanisms of resistance, could serve as a therapeutic strategy to control or delay the progression of the disease and therefore improve the quality of life of the patient.
    VL  - 6
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • Department of Cell Biology, Histology and Pharmacology, Faculty of Physiotherapy, University of Valladolid, Soria, Spain

  • Department of Cell Biology, Histology and Pharmacology, Faculty of Physiotherapy, University of Valladolid, Soria, Spain

  • Sections