Анотація
Актуальність. Колоректальний рак (КР) одне з найбільш частих злоякісних новоутворень у світі. Він займає третє місце в структурі онкологічної захворюваності друге – в структурі смертності. Одним з важливих факторів, що призводять до КР, є хронічне запалення кишківника, вирішальну роль в якому відіграють прозапальні цитокіни. Серед прозапальних цитокінів інтерлейкін-6 посідає одне з провідних місць у патогенезі КР. Отже актуальним є з’ясування ролі інтерлейкіну-6 (IL-6) у розвитку та прогресуванні КР, визначення діагностичної та прогностичної цінності цитокіну та аналіз застосування терапевтичних стратегій, спрямованих на сигнальний шлях IL-6, при КР. Мета роботи – проаналізувати роль прозапального цитокіну IL-6 у розвитку колоректального раку, розглянути механізми онкогенної дії цитокіну, оцінити результати застосування терапевтичних стратегій, спрямованих на сигнальний шлях IL-6 при колоректальному раку та охарактеризувати прогностичну та діагностичну цінність IL-6. Матеріали та методи. Пошук даних для огляду проводили в базах даних Pubmed, Cochrane Library, ScienceDirect. Проаналізовано результати досліджень, виконаних до травня 2021 року. Відповідні неопубліковані дослідження виявлено у реєстрі клінічних випробувань Національних інститутів здоров’я США www.clinicaltrials.gov. Результати та їх обговорення. Дано оцінку діагностичної та прогностичної цінності IL-6 у хворих на КР. Висвітлено механізми регуляції IL-6 росту пухлини, ангіогенезу, апоптозу, метастазування при КР. Наведено результати доклінічного і клінічного тестування моноклональних антитіл до ІL-6, ІL-6R, низькомолекулярних сполук, що впливають на цитокінову рецепторну передачу сигналів через gp130 та JAK-STAT, а також лікарських препартів та сполук природного походження, які здатні чинити інгібіторну дію на IL-6/STAT3 сигнальний шлях. Висновки. Стратегії, спрямовані на блокування передачі сигналів IL-6, можуть бути потенційно корисні у разі злоякісних новоутворень, передусім як компонент комбінованої терапії, або для того, щоб запобігти несприятливим симптомам, пов’язаним з імунотерапією раку. Подальші дослідження необхідні для остаточного з’ясування ролі класичної передачі сигналу IL-6 і транс-сигналінгу у патогенезі колоректального раку, оскільки це може створити підґрунтя для більш цілеспрямованого пригнічення функцій цього плейотропного цитокіну.
Посилання
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