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The challenge of drug resistance in cancer treatment: a current overview

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Abstract

It is generally accepted that recent advances in anticancer agents have contributed significantly to the improvement of both the disease-free survival and quality of life in cancer patients. However, in many instances, a favorable initial response to treatment changes afterwards, thereby leading to cancer relapse and recurrence. This phenomenon of acquired resistance to therapy, it is a major problem for totally efficient anticancer therapy. The failure to obtain an initial response reflects a form of intrinsic resistance. Specific cell membrane transporter proteins are implicated in intrinsic drug resistance by altering drug transport and pumping drugs out of the tumor cells. Moreover, the gradual acquisition of specific genetic and epigenetic abnormalities in cancer cells could contribute greatly to acquired drug resistance. A critical issue in the clinical setting, is that the problem of drug resistance appears to have a negative effect on also the new molecularly-targeted anticancer drugs. Several ongoing efforts are being made by the medical community aimed to the identification of such resistance mechanisms and the development of novel drugs that could overcome them. In this review, the major drug resistance mechanisms and strategies to overcome them are critically discussed, and also possible future directions are suggested.

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Abbreviations

MDR:

Multidrug resistance

ABC:

Adenosine triphosphate-binding cassette

DHFR:

Dihydrofolate reductase

NER:

Nucleotide excision repair

MTD:

Maximum tolerated dose

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Acknowledgements

Dr. A.G. Georgakilas acknowledges funding from DAAD Grant “DNA Damage and Repair and Their Relevance to Carcinogenesis” (No. 57339330).

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Authors and Affiliations

  1. Department of Internal Medicine, Oncology Unit, Hippokrateio Hospital, University of Athens, Athens, Greece

    Michail Nikolaou

  2. Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, 35340, Izmir, Turkey

    Athanasia Pavlopoulou

  3. DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), 15780, Athens, Greece

    Alexandros G. Georgakilas

  4. 1st Department of Otolaryngology Head and Neck Surgery, Hippokrateio Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece

    Efthymios Kyrodimos

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  1. Michail Nikolaou
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Nikolaou, M., Pavlopoulou, A., Georgakilas, A.G. et al. The challenge of drug resistance in cancer treatment: a current overview. Clin Exp Metastasis 35, 309–318 (2018). https://doi.org/10.1007/s10585-018-9903-0

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