Molecular mechanisms of tumor drug resistance

DOI: https://doi.org/10.29296/24999490-2023-02-01

E.V. Okladnikova, I.S. Zinchenko, T.G. Ruksha
Professor V. F. Voino-Yasenetsky Krasnoyarsk State Medical University,
Partizana Zheleznyaka str., 1, Krasnoyarsk, 660022, Russian Federation

Introduction. Overcoming resistance to anticancer drugs in the treatment of malignant neoplasms is an urgent problem of recent decades. Unfortunately, there is no single mechanism for the development of resistance. Alterations that occur in a normal cell during its transformation into a malignant one can lead to the development of primary resistance whereas secondary resistance occurs already as a result of treatment with anticancer drugs. The purpose of the review. To summarize current data on the mechanisms of a drug resistance development to chemotherapeutic agents in order to select and implement possible ways to overcome it. Material and methods. The materials were the results of research on this topic over the past 15 years, from 2007 to 2022. The publications included in the databases PubMed, Medline, EMBASE were analyzed. Results. Analysis of the research results showed that among the mechanisms of a drug resistance development, there are changes in the activity of energy and metabolic processes, structural and/or functional alterations in the expression and function of cancer-related genes and proteins. All together it can lead to a disruption in the flow of the drug into the cancer cell, its active removal from the cell and the patient’s body, an insufficient, short-lived or perverted reaction of the malignant tumor to the drug. At the same time, the heterogeneity of primary tumor cells and metastatic cells leads to multiple mechanisms of drug resistance development in the same patient or in different patients with the same histological type of tumor. Overcoming or blocking some mechanisms of resistance can lead to the development of others. Conclusion. The study of the cancer cell drug resistance will help to optimize pharmacotherapy and improve the quality and life expectancy of patients suffering from cancer.
Keywords: 
drug resistance, аntitumor drug resistance, pathogenesis of drug resistance, chemotherapy
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