Молекулярные мишени немелколеточного рака легкого (НМРЛ) вне «главной тройки»

Рак легкого (РЛ) занимает первое место в структуре общей онкологической заболеваемости и смертности у мужчин как в России, так и в зарубежных странах. Большинство новых случаев РЛ диагностируется у пациентов старше 65 лет, и в последние годы наблюдается тенденция к увеличению данного показателя. РЛ представляет собой гетерогенную группу злокачественных опухолей с различными генетическими и биологическими характеристиками. Несмотря на то, что курение считается основной причиной немелкоклеточного рака легкого (НМРЛ), генетическая предрасположенность и воздействие окружающей являются причиной развития 10–15 % случаев заболевания. Тактика лечения пациентов с одним НМРЛ давно отработана и, как правило, не вызывает никаких трудностей. Хирургическое вмешательство является основным методом лечения ранних стадий НМРЛ. Однако, по мере прогрессирования заболевания возрастает риск метастазирования, и в этом случае эффективность хирургического метода лечения резко снижается. Разработка новых схем лекарственной терапии, использование таргетных препаратов улучшила выживаемость больных с РЛ, несущими онкогенные драйверные мутации. Персонифицированное лечение становится все более доступным по мере развития технологии секвенирования. Таргетная терапия несомненно улучшает исходы больных НМРЛ, опухоли которых несут онкогенные драйверные мутации EGFR, слияние АLK и реаранжировки ROS1. Однако, помимо основных молекулярных мишеней, выявлены и изучаются другие генетические альтерации, такие как: вирусный онкоген Kirsten RAS (КРАS), МЕТ, RЕТ, HER2 и NRG. Некоторые из таких мутаций (BRAF и NTRK) уже доступны для таргетной терапии. Перечень генетических альтераций растет и расширяется молекулярное профилирование больных НМРЛ, что имеет весьма важное значение при прогрессировании заболевания. Молекулярно-генетический отбор идентифицирует конкретные группы пациентов, которые получают пользу от таргетной терапии и дает представление о потенциальных механизмах резистентности. Несмотря на достигнутый прогресс, необходимы дальнейшие исследования для выяснения взаимодействий с иммунными клетками в микроокружении опухоли как факторов, влияющих на выживаемость. Кроме того, становится все более важным изучение таргетной терапии в контексте мультимодального лечения. Настоящий обзор посвящен пониманию генетических изменений, поиску новых генетических мишеней, проблемам и будущим направлениям развития таргетной терапии в лечении пациентов с опухолями легких.

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