Потенциальные мишени гепарина при прогрессировании и метастазировании злокачественных новообразований

Онкологические заболевания занимают одну из лидирующих позиций в структуре смертности населения. Комплексный подход в онкотерапии, помимо прямого воздействия на злокачественные опухоли, направлен на снижение рисков их рецидивов и метастазирования, а также снижение тяжести побочных эффектов противоопухолевой химио- и радиотерапии заболевания. При онкологических заболеваниях повышается вязкость крови, что сопровождается гиперкоагуляционным синдромом. Для преодоления его последствий активно используются прямые и непрямые антикоагулянты, в частности гепарин и его производные. Биологические функции и структурные особенности гепарина делают его потенциальной универсальной платформой в разработке препаратов для широкого применения, в том числе в онкологии. Появление технологии фракционирования гепаринов и получения низкомолекулярных форм и их производных позволило сосредоточиться не только на антикоагуляционных эффектах, но и получать фракции с целевой фармакологической активностью. Применение антикоагулянтов в некоторых случаях позволило выявить их противоопухолевый эффект, что послужило основанием для более детального исследования фармакотерапевтических эффектов этой группы препаратов. В настоящее время получены данные о множественных путях взаимодействия гепарина и опухолевых клеток. В процессе развития первичной опухоли и при формировании вторичных метастазов в отдаленных органах есть ряд общих черт, обусловленных использованием одних и тех же молекулярно-клеточных механизмов. В качестве мишеней для гепарина здесь могут выступать молекулы, отвечающие за межклеточные взаимодействия как между опухолевыми клетками, так и между клетками опухоли и опухоль ассоциированными иммунокомпетентными клетками, преимущественно лимфоцитами и макрофагами, что способствует уходу опухоли от иммунного надзора. Другой важной мишенью являются цитокины, стимулирующие опухолевый ангиогенез. Производные гепарина способны подавлять активность опухолей и нарушать процессы метастазирования на различных этапах, ингибируя активность гепараназы, P-/L-селектина, ангиогенез, модулируя хемокиновую ось CXCL12-CXCR4, регулируя активность ОАМ.

Данный краткий обзор рассматривает реальные контуры понимания и использования потенциальных антиметастатических свойств гепарина и его производных при злокачественных новообразованиях костной ткани, поскольку препараты на основе гепарина применяются в качестве антикоагулянтов при эндопротезировании крупных суставов и дефектов кости у больных остеосаркомой.

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