Причины резистентности к PARP-ингибированию и возможности ее преодоления. Клинический случай агрессивного течения BRCA-ассоциированного рака молочной железы
https://doi.org/10.17650/1994-4098-2022-18-1-54-65
Аннотация
На сегодняшний день опции терапии BRCA-ассоциированного рака молочной железы существенно расширились с появлением нового класса препаратов – PARP-ингибиторов. Однако, несмотря на доказанную противоопухолевую эффективность препаратов, в клинической практике приобретенная резистентность к PARP-ингибиторам приводит к затруднениям в подборе дальнейшей терапии ввиду отсутствия понимания причин резистентности и алгоритма действий. Несмотря на различные механизмы резистентности к PARP-ингибиторам, выбор последующей комбинированной терапии после выявления резистентности к PARP-ингибиторам должен основываться на понимании этих механизмов и существовании гетерогенности метастатического процесса. При этом весьма важно изучать молекулярно-генетические характеристики заболевания на каждом этапе прогрессирования, что поможет выявить причину резистентности и подобрать оптимальную стратегию лечения. Вероятно, выполнение жидкостной биопсии по циркулирующей опухолевой дНК, детекция циркулирующих опухолевых клеток, циркулирующей микроРНК или экзосом могут быть более подходящими методами молекулярной диагностики, чем повторные биопсии. В настоящий момент есть данные о выявлении 2 типов резистентности к PARP-ингибиторам, включающих причины, не зависящие и зависящие от гена BRCA1/2 и механизма репарации путем гомологичной рекомбинации дНК (HRR). стратегии использования комбинаций различных терапевтических режимов совместно с PARP-ингибиторами являются весьма обнадеживающими опциями для предупреждения резистентности к терапии ввиду все возрастающего числа пациентов с подобным клиническим течением заболевания.
В представленном клиническом случае BRCA1-ассоциированный тройной негативный рак молочной железы демонстрирует агрессивное клиническое течение при отказе от адъювантной химиотерапии. также описана эффективность терапии PARP-ингибитором олапарибом при диссеминированном BRCA1-мутированном раке молочной железы, в том числе с метастазами в головной мозг. При этом на фоне хорошей переносимости и контроля над заболеванием, особенно в случае метастазов в головной мозг, применение PARP-ингибитора олапариба составляет достойную альтернативу химиотерапевтическим режимам. Подбор последующей терапии после PARP-ингибитора требует взвешенного подхода именно с учетом возможных причин перекрестной резистентности с химиотерапевтическими режимами.
Об авторах
А. И. СтуканьРоссия
Анастасия Игоревна Стукань
350040 Краснодар, ул. Димитрова, 146;
350063 Краснодар, ул. Митрофана Седина, 4
А. Ю. Горяинова
Россия
350040 Краснодар, ул. Димитрова, 146;
350063 Краснодар, ул. Митрофана Седина, 4
С. В. Шаров
Россия
350040 Краснодар, ул. Димитрова, 146
О. А. Гончарова
Россия
350040 Краснодар, ул. Димитрова, 146
З. К. Хачмамук
Россия
350040 Краснодар, ул. Димитрова, 146
В. В. Дуров
Россия
350040 Краснодар, ул. Димитрова, 146
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Рецензия
Для цитирования:
Стукань А.И., Горяинова А.Ю., Шаров С.В., Гончарова О.А., Хачмамук З.К., Дуров В.В. Причины резистентности к PARP-ингибированию и возможности ее преодоления. Клинический случай агрессивного течения BRCA-ассоциированного рака молочной железы. Опухоли женской репродуктивной системы. 2022;18(1):54-65. https://doi.org/10.17650/1994-4098-2022-18-1-54-65
For citation:
Stukan A.I., Goryainova A.Yu., Sharov S.V., Goncharova O.A., Khachmamuk Z.K., Durov V.V. Causes of resistance to PARP inhibitors and ways to overcome it. Case report of aggressive BRCA-related breast cancer. Tumors of female reproductive system. 2022;18(1):54-65. (In Russ.) https://doi.org/10.17650/1994-4098-2022-18-1-54-65