Mechanisms of Multidrug Resistance in Cancer Chemotherapy

By K. Bukowski, M. Kciuk, R. Kontek. International Journal of Molecular Sciences, 2020

1,430 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/371e44b8d72cb32e2df0b54ea36c144300ec1c82

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In Molecular Biology

In Oncology

K. Guan

Citations in the corpus

Doxorubicin—An Agent with Multiple Mechanisms of Anticancer Activity (2023, background): “Topoisomerase I inhibitors, such as irinotecan and topotecan, and topoisomerase II inhibitors, such as etoposide, teniposide, and anthracyclines (idarubicin, daunorubicin, and doxorubicin (DOX)), induce DNA strand breaks and hinder the action of topoisomerases that are involved in the DNA replicatio”
The Hippo signalling pathway and its implications in human health and diseases (2022, background): “The increased ef ﬂ ux and metabolic conversion of a drug will decrease its ef ﬁ cacy considerably by reducing intracellular drug concentrations 267 .”
Regulated cell death (RCD) in cancer: key pathways and targeted therapies (2022, background): “The emergence of multidrug resistance (MDR) was a major obstacle to treating cancer diseases.(137) Studies have shown that NFκB could increase the expression of the MDR1 gene, and then inhibition of NF-κB activity could enhance the sensitivity of drugresistant cancer cells to chemotherapy drugs.”