Molekulyarnaya Meditsina (Molecular medicine)Molekulyarnaya Meditsina (Molecular medicine)Молекулярная медицина1728-29182499-9490Russkiy Vrach Publishing House34081310.29296/24999490-2023-02-01ReviewsОбзорыReview ArticleMolecular mechanisms of tumor drug resistanceМолекулярные механизмы лекарственной устойчивости опухолейhttps://orcid.org/0000-0002-1909-222XOkladnikovaEvgenja V.ОкладниковаЕвгения Владимировна
Russian Federation

associated professor of Pathophysiology Department, candidate of medical sciences

доцент кафедры патологической физиологии им. В.В. Иванова, кандидат медицинских наук

farmasis@yandex.ruhttps://orcid.org/0000-0001-7085-6304ZinchenkoIvan S.ЗинченкоИван Сергеевич
Russian Federation

PhD student of the Pathophysiology Department

аспирант кафедры патологической физиологии им. В.В. Иванова

zinchenko.ivan.003@gmail.comhttps://orcid.org/0000-0001-8142-4283RukshaTatiana G.РукшаТатьяна Геннадьевна
Russian Federation

Head of the Pathophysiology Department, doctor of medical sciences

заведующая кафедрой патологической физиологии им. В.В. Иванова, доктор медицинских наук, профессор

tatyana_ruksha@mail.ruProfessor V. F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityФГБОУ ВО «Красноярский государственный медицинский университет им. проф. В.Ф. Войно-Ясенецкого» Министерства здравоохранения Российской Федерации210420232123101804202318042023Copyright ©; 2023, Russkiy Vrach Publishing HouseCopyright ©; 2023, ИД "Русский врач"2023Russkiy Vrach Publishing HouseИД "Русский врач"https://journals.eco-vector.com/1728-2918/article/view/340813

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.

Введение. Преодоление устойчивости к противоопухолевым препаратам при лечении злокачественных новообразований является актуальной проблемой последних десятилетий. К сожалению, нет какого-то единого механизма развития резистентности. Изменения, возникающие в здоровой клетке при трансформации ее в злокачественную, могут приводить к развитию первичной резистентности, а вторичная резистентность происходит уже как результат лечения химиотерапевтическими препаратами.

Цель обзора. Обобщить современные данные о механизмах развития лекарственной устойчивости к химиотерапевтическим средствам при лечении злокачественных новообразований с целью выбора и реализации возможных путей ее преодоления.

Материал и методы. Материалами послужили результаты исследований по данной теме за последние 15 лет, с 2007 по 2022 годы. Анализировались публикации, входящие в базы данных PubMed, Medline, EMBASE.

Результаты. Анализ результатов исследований показал, что среди механизмов развития лекарственной устойчивости выделяют изменения активности энергетических и метаболических процессов, структурные и(или) функциональные изменения экспрессии и функции генов и белков опухолевой клетки. Все это может приводить к нарушению поступления лекарственного вещества в клетку опухоли, его активному выведению из клетки и организма пациента, недостаточной, непродолжительной или извращенной реакции злокачественной опухоли на лекарственный препарат. При этом гетерогенность клеток опухоли и клеток ее метастазов приводит к возможности существования одновременно нескольких механизмов лекарственной резистентности у одного и того же пациента или у разных пациентов с одним гистологическим типом опухоли. Преодоление или устранение одних механизмов резистентности может приводить к развитию других.

Заключение. Изучение механизмов развития резистентности к противоопухолевым препаратам позволит оптимизировать фармакотерапию и улучшить качество и продолжительность жизни пациентов, страдающих онкологическими заболеваниями.

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