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.
Highlights
Cancer is responsible for about 1 in 6 deaths worldwide
We have presented the latest data on the mechanisms of cellular resistance to chemotherapy and chemotherapeutics currently used in clinical treatment as well as on the mechanisms of action of novel potential anticancer agents which have been designed to overcome these resistance mechanisms
The development of Multidrug resistance (MDR) is a complex process associated with enhanced efflux of drugs, elevated metabolism of xenobiotics, increased DNA repair capacity, growth and genetic factors, or any combination of these mechanisms
Summary
Cancer is responsible for about 1 in 6 deaths worldwide. Factors that are associated with elevated risk of cancer are tobacco use (22% of cancer deaths), lack of physical activity, alcohol use, low vegetable and fruit intake, and high body mass index. These factors are thought to be responsible for approximately one third of cancer deaths. Despite the fact that there are several different methods of cancer treatments, including radiation therapy, surgery, immunotherapy, endocrine therapy, and gene therapy, chemotherapy still remains the most common method of cancer healing. We have presented the latest data on the mechanisms of cellular resistance to chemotherapy and chemotherapeutics currently used in clinical treatment as well as on the mechanisms of action of novel potential anticancer agents which have been designed to overcome these resistance mechanisms
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