Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 May 2;21(9):3233.
doi: 10.3390/ijms21093233.

Mechanisms of Multidrug Resistance in Cancer Chemotherapy

Karol Bukowski  1 , Mateusz Kciuk  1 , Renata Kontek  1
Affiliations
Review

Mechanisms of Multidrug Resistance in Cancer Chemotherapy

Karol Bukowski et al. Int J Mol Sci. .

Abstract

Cancer is one of the main causes of death worldwide. Despite the significant development of methods of cancer healing during the past decades, chemotherapy still remains the main method for cancer treatment. Depending on the mechanism of action, commonly used chemotherapeutic agents can be divided into several classes (antimetabolites, alkylating agents, mitotic spindle inhibitors, topoisomerase inhibitors, and others). Multidrug resistance (MDR) is responsible for over 90% of deaths in cancer patients receiving traditional chemotherapeutics or novel targeted drugs. The mechanisms of MDR include elevated metabolism of xenobiotics, enhanced efflux of drugs, growth factors, increased DNA repair capacity, and genetic factors (gene mutations, amplifications, and epigenetic alterations). Rapidly increasing numbers of biomedical studies are focused on designing chemotherapeutics that are able to evade or reverse MDR. The aim of this review is not only to demonstrate the latest data on the mechanisms of cellular resistance to anticancer agents currently used in clinical treatment but also to present the mechanisms of action of novel potential antitumor drugs which have been designed to overcome these resistance mechanisms. Better understanding of the mechanisms of MDR and targets of novel chemotherapy agents should provide guidance for future research concerning new effective strategies in cancer treatment.

Keywords: DNA repair; P-glycoprotein; cancer; chemotherapeutics; drug metabolism; epigenetic alterations; growth factors; inhibitors; microRNA; multidrug resistance.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Classification of commonly used chemotherapeutics depending on their mechanism of action [7,8,9].
Figure 2
Figure 2
Mechanisms of chemotherapeutic drug resistance in cancer cells [9,13,14,15,16].
Figure 3
Figure 3
Differences in TP53 gene expression level between normal (a) and cancer cells (b) and consequences thereof: (a) accurate level of expression of TP53 gene and (b) decreased level of expression of TP53 gene [38].
Figure 4
Figure 4
Cancer cell gene regulation by epigenetic alterations [50,51,52].
See this image and copyright information in PMC

References

    1. Global Burden of Disease Cancer Collaboration. Fitzmaurice C., Allen C., Barber R.M., Barregard L., Bhutta Z.A., Brenner H., Dicker D.J., Chimed-Orchir O., Dandona R., et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3:524–548. - PMC - PubMed
    1. WHO. [(accessed on 12 September 2018)]; Available online: https://www.who.int/news-room/fact-sheets/detail/cancer.
    1. Kikuchi H., Yuan B., Hu X., Okazaki M. Chemopreventive and anticancer activity of flavonoids and its possibility for clinical use by combining with conventional chemotherapeutic agents. Am. J. Cancer Res. 2019;9:1517–1535. - PMC - PubMed
    1. Lichota A., Gwozdzinski K. Anticancer Activity of Natural Compounds from Plant and Marine Environment. Int. J. Mol. Sci. 2018;19:11. doi: 10.3390/ijms19113533. - DOI - PMC - PubMed
    1. Marchi E., O’Connor O.A. Safety and efficacy of pralatrexate in the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. Ther. Adv. Hematol. 2012;3:227–235. doi: 10.1177/2040620712445330. - DOI - PMC - PubMed

MeSH terms

Substances