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摘要
Анализ литературы, имеющей отношение к фенотипической пластичности трансформированных клеток при развитии резистентности опухолей к терапии, привел с учетом основных характеристик эпителиального, мезенхимального, стволового и сенесцентного состояний опухолевых клеток к выводу, что ключевым фактором терапевтической резистентности является обратимость переходов между этими состояниями. Молекулярные механизмы таких переходов могут включать стохастические переключения активных генов между участием и неучастием в транскрипции. Кинетика переходов и соответствующее равновесие между разными фенотипическими состояниями существенно зависят от среды, где это происходит, а значит от возраста опухоленосителя и от его гормонально-метаболического статуса. Таким образом, воздействия на метаболические параметры организма могут влиять на эффективность противоопухолевой терапии без изменений жизнеспособности и пролиферации опухолевых клеток в любом из возможных для них состояний. С таких позиций рассмотрены данные о противоопухолевых эффектах антидиабетических бигуанидов. Сделан вывод, что, если анализировать в терминах обратимости фенотипических состояний трансформированных клеток противоопухолевые эффекты воздействий, цитотоксические или цитостатические последствия которых неочевидны, это может не только помочь в понимании того, каким образом такие воздействия могут влиять на опухоли, но и расширить круг критериев для поисков новых противораковых средств.
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