Современное лечение ALK- позитивного немелкоклеточного рака легкого

Рак легкого (РЛ) занимает первое место в структуре общей онкологической заболеваемости мужского населения. Ежегодно в мире РЛ диагностируется более чем у 1,8 миллиона человек и остается основной причиной смертности от злокачественных новообразований как в развивающихся, так и в развитых странах, а 5 летняя выживаемость, достигающая 19 % вызывает разочарование. Подобные неудовлетворительные исходы объясняются многими факторами, включая диагностику РЛ на поздней стадии, когда излечение остается редким при доступных на сегодняшний день методах лечения. Немелкоклеточный рак легкого (НМРЛ) с хромосомной перестройкой киназы анапластической лимфомы (ALK) чувствителен к таргетной терапии ингибиторами тирозинкиназы (ТКИ). Опухолевые клетки, содержащие слияние ALK, чувствительны к ингибиторам TKИ – таргетным препаратам, которые существенно улучшили результаты лечения больных ALK-позитивным НМРЛ, половина из которых выживают более 6,8 года после установления диагноза. Количество пациентов с ALK-позитивным НМРЛ варьируется, так ALK реаранжировки обнаруживаются примерно в 3–7 % аденокарцином легкого, что составляет до 60 000 новых случаев заболевания ежегодно во всем мире. ALK-позитивный НМРЛ наблюдается почти исключительно при аденокарциномах, ассоциированных с лицами более молодого возраста, мужского пола и никогда не курившими или курившими мало. Больным ALK-позитивным НМРЛ I–III стадии показано лечение аналогичное пациентам с НМРЛ дикого типа, включая хирургическое вмешательство, лучевую терапию, химиотерапию или мультимодальное лечение в зависимости от стадии опухолевого процесса. В последние десятилетие разработано несколько ALK ТКИ и среди них алектиниб, который в настоящее время является препаратом выбора первой линии терапии больных, не получавших лечения. Изучение механизмов резистентности привело к разработке ингибиторов ALK следующего поколения, которые лучше проникают в центральную нервную систему, активно воздействуя на метастазы в головном мозге. Данный обзор освещает современное состояние и перспективы развития терапии ALK-позитивного НМРЛ.

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