Biopolym. Cell. 2012; 28(2):83-92.
Огляди
Сучасні підходи до покращеня протипухлинної хіміотерапії з використанням алкілувальних сполук: стан проблеми в світі та в Україні
1Яцишина А. П.
  1. Інститут молекулярної біології і генетики НАН України
    вул. Академіка Заболотного, 150, Київ, Україна, 03680

Abstract

Aлкілувальні сполуки часто застосовують у хіміотерапії раку. Вони алкілують геномну ДНК по багатьох сайтах. Алкілування гуаніну в позиції О6 цитотоксичне, має найсильніший мутагенний потенціал, а також може спричиняти розвиток вторинних пухлин. Алкільні групи у позиції O6 гуаніну видаляються за допомогою репаративного ферменту O6-метилгуанін-ДНК метилтрансферази (MGMT). Ефективність хіміотерапії з використанням O6алкілувальних сполук обмежена експресією MGMT у ракових клітинах та шкідливим побічним токсичним впливом у нормальних клітинах. Наразі для покращення хіміотерапії раку розробляють різні підходи до модуляції експресії та активності MGMT. До них належать два головних напрямки, а саме – підвищення хіміочутливості ракових клітин до алкілувальних ліків і захист нормальних клітин від токсичної дії хіміотерапії. Огляд зосереджено на існуючих спробах покращити хіміотерапію злоякісних пухлин за допомогою алкілувальних сполук як у світі, так і в Україні.
Keywords: хіміотерапія раку, стратегії покращення хіміотерапії, алкілувальні сполуки, O6-метилгуанін-ДНК метилтрансфераза (MGMT), репарація ДНК

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