medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-4S-44-50medsovet-6210Research ArticleОНКОУРОЛОГИЯONCOUROLOGYНовые подходы к лечению кастрационно- резистентного рака предстательной железы: ингибиторы PARPThe new approaches to the treatment of castration- resistant prostate cancer: PARP inhibitorshttps://orcid.org/0000-0002-5160-925XГрицкевичА. А.GritskevichА. А.

Грицкевич Александр Анатольевич, д.м.н., старший научный сотрудник отделения урологии

117997, Москва, ул. Большая Серпуховская, д. 27 

Alexander A. Gritskevich, Dr. Sci. (Med.), Senior Researcher of the Urology Department

27, Bolshaya Serpukhovskaya St., Moscow, 117997

grekaa@mail.ruhttps://orcid.org/0000-0002-0945-2498РусаковИ. Г.RusakovI. G.

Русаков Игорь Георгиевич, д.м.н., профeccор, заместитель главного врача по онкологии

105077, Москва, ул. 11-я Парковая, д. 32  

Igor G. Rusakov, Dr. Sci. (Med.), Professor, Deputy Chief Physician on Oncology, Pletnev State Clinical Hospital

32, 11 Parkovaya St., Moscow, 105077

https://orcid.org/0000-0002-3646-1664БайтманТ. П.BaitmanТ. Р.

Байтман Татьяна Павловна, аспирант отделения урологии

117997, Москва, ул. Большая Серпуховская, д. 27 

Tatiana P. Baitman, Graduate Student of the Urology Department, Vishnevsky National Medical Research Center of Surgery

27, Bolshaya Serpukhovskaya St., Moscow, 117997

https://orcid.org/0000-0002-6751-2399МишугинС. В.MishuginS. V.

Мишугин Сергей Владимирович, к.м.н., заведующий отделением онкоурологии

105077, Москва, ул. 11-я Парковая, д. 32

Sergey V. Mishugin, Cand. Sci. (Med.), Head of the Oncourological Department

32, 11 Parkovaya St., Moscow, 105077

Национальный медицинский исследовательский центр хирургии имени А.В. ВишневскогоRussian FederationГородская клиническая больница имени Д.Д. ПлетнёваРоссияPletnev State Clinical HospitalRussian Federation20211206202104S4450Copyright © Грицкевич А.А., Русаков И.Г., Байтман Т.П., Мишугин С.В., 20212021Грицкевич А.А., Русаков И.Г., Байтман Т.П., Мишугин С.В.Gritskevich А.А., Rusakov I.G., Baitman Т.Р., Mishugin S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6210

Рак предстательной железы (РПЖ) – одна из ведущих причин онкологической смертности мужского населения. В настоящее время патогенез РПЖ достаточно подробно изучен, что делает возможным в большинстве случаев успешное радикальное лечение. Однако примерно у 30% пациентов традиционные методики (радикальная простатэктомия, лучевая терапия, андрогенная депривационная терапия и др.) неэффективны: развивается кастрационно- резистентный (КРРПЖ) и метастатический (мРПЖ) рак предстательной железы. Благодаря достижениям современной молекулярной онкологии сегодня известны «обходные пути», генетические и эпигенетические сочетания, позволяющие РПЖ прогрессировать, несмотря на отсутствие андрогенной стимуляции. Персонализированный подход в онкологии, постепенно входящий в стандарты терапии мКРРПЖ, позволяет не только своевременно выявить специфические мутации, но и верно подобрать наиболее эффективную при них терапию. В настоящее время наиболее перспективными группами лекарственных средств для лечения мКРРПЖ являются ингибиторы поли(АДФ-рибоза)-полимеразы (PARP), блокаторы иммунных контрольных точек и вещества, тропные к мембране простатспецифического антигена (ПСА), – PSMA-таргетная терапия. В статье предпринята попытка суммировать актуальные данные об ингибиторах PARP. Препараты этой группы, наиболее эффективные в отношении злокачественных новообразований с мутациями в генах BRCA1/2 и успешно применяемые при раке яичников, молочной железы и поджелудочной железы, были одобрены для лечения мКРРПЖ не так давно. Появление молекулярно- генетических тестов позволило сделать лечение мКРРПЖ более персонализированным. В настоящее время проводятся исследования эффективности ингибиторов PARP при других генетических и эпигенетических изменениях, а также в сочетании с иными терапевтическими препаратами. 

Prostate cancer (PC) is one of the leading causes of cancer death in the male population. Currently, the pathogenesis of prostate cancer has been studied in sufficient detail, which makes a successful radical treatment possible in most cases. However, in about 30% of patients traditional methods (e.g., radical prostatectomy, radiation therapy, androgen deprivation therapy – ADT, etc.) are ineffective, and castration- resistant (CRPC) and metastatic (mPC) types of РС are developing. Due to the advances in modern molecular oncology, various “workarounds”, genetic and epigenetic combinations, that allow РС to progress despite the absence of androgenic stimulation, are known nowadays. A personalized approach in oncology, which gradually becomes one of the standards for mCRPC therapy, allows not only to identify specific mutations, but also to select the most effective therapy for them in the most correct way. Now the most promising groups of the drugs for mCRPC treatment are poly(ADP-ribose)-polymerase (PARP) inhibitors, immune checkpoint inhibitors, and prostate- specific membrane antigen (PSMA) targeted therapy. This article attempts to summarize the current data on PARP inhibitors. The drugs of this group are especially effective for malignant neoplasms with mutations in the BRCA 1/2 genes, and successfully used in ovarian, breast and pancreatic cancer. They have been approved for the treatment of mCRPC a not so long ago. The advent of personalized companion tests has made the treatment of mCRPC more precise. Nowadays studies on the effectiveness of PARP inhibitors for mCRPC with other genetic and epigenetic changes, as well as in combination with other therapeutic agents, are notably actual. 

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The authors declare that there are no conflicts of interest present.