surgoncoКреативная хирургия и онкологияCreative surgery and oncology2076-30932307-0501Башкирский государственный медицинский университет10.24060/2076-3093-2022-12-1-48-55surgonco-674Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSПерспективы PARP-ингибиторов при лечении BRCA-ассоциированного рака поджелудочной железы. Обзор литературыProspects of PARP Inhibitors in Treatment of BRCA-Mutated Pancreatic Cancer: a Literature Reviewhttps://orcid.org/0000-0003-3734-2779МеньшиковК. В.MenshikovK. V.

к.м.н., доцент, кафедра онкологии с курсами онкологии и патологической анатомии ИДПО, отдел химиотерапии, 

Республика Башкортостан, Уфа

Cand. Sci. (Med.), Assoc. Prof., Department of Oncology with сourses of Oncology and Pathological Anatomyfor Advanced Professional Education, Chemotherapy Unit,

Ufa

kmenshikov80@bk.ruhttps://orcid.org/0000-0003-0996-5995СултанбаевА. В.SultanbaevA. V.

к.м.н., отдел противоопухолевой лекарственной терапии, 

Республика Башкортостан, Уфа

Cand. Sci. (Med.), Anticancer Drug Therapy Unit, 

Ufa

https://orcid.org/0000-0003-1185-977XМусинШ. И.MusinSh. I.

к.м.н., хирургическое отделение № 6, 

Республика Башкортостан, Уфа

Cand. Sci. (Med.), Surgery Unit No. 6,

Ufa

https://orcid.org/0000-0002-8461-9243ИзмайловА. А.IzmailovA. A.

д.м.н., доцент, кафедра урологии с курсом ИДПО, 

Республика Башкортостан, Уфа

Dr. Sci. (Med.), Assoc. Prof., Department of Urology with a course of Advanced Professional Education, 

Ufa

https://orcid.org/0000-0002-8665-8895МеньшиковИ. А.MenshikovaI. A.

к.м.н., доцент, кафедра биологической химии, 

Республика Башкортостан, Уфа

Cand. Sci. (Med.), Assoc. Prof., Department of Biological Chemistry,

Ufa

https://orcid.org/0000-0001-5926-0446СултанбаеваН. И.SultanbaevaN. I.

отделение противоопухолевой лекарственной терапии № 1, 

Республика Башкортостан, Уфа

Anticancer Drug Therapy Unit No. 1, 

Ufa

https://orcid.org/0000-0003-1242-759XПоповаЕ. В.PopovaE. V.

отделение амбулаторной противоопухолевой лекарственной терапии, 

Республика Башкортостан, Уфа

Outpatient Anticancer Drug Therapy Unit,

Ufa

https://orcid.org/0000-0003-4458-694XХамматоваЛ. А.KhammatovaL. A.

Республика Татарстан, Казань

Kazan

Республиканский клинический онкологический диспансер; Башкирский государственный медицинский университетРоссияRepublican Clinical Oncology Dispensary; Bashkir State Medical UniversityRussian FederationРеспубликанский клинический онкологический диспансерРоссияRepublican Clinical Oncology DispensaryRussian FederationБашкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian FederationДетская городская поликлиника № 9РоссияChildren’s City Polyclinic No. 9Russian Federation2022010620221214855Copyright © Меньшиков К.В., Султанбаев А.В., Мусин Ш.И., Измайлов А.А., Меньшиков И.А., Султанбаева Н.И., Попова Е.В., Хамматова Л.А., 20222022Меньшиков К.В., Султанбаев А.В., Мусин Ш.И., Измайлов А.А., Меньшиков И.А., Султанбаева Н.И., Попова Е.В., Хамматова Л.А.Menshikov K.V., Sultanbaev A.V., Musin S.I., Izmailov A.A., Menshikova I.A., Sultanbaeva N.I., Popova E.V., Khammatova L.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surgonco.ru/jour/article/view/674

Аденокарцинома поджелудочной железы имеет 5-летнюю общую выживаемость 9 %, а к 2030 году, по прогнозам, эта опухоль станет второй ведущей причиной смертности от онкологических заболеваний в США. Семейный рак поджелудочной железы и синдромы генетической предрасположенности стали областью повышенного интереса из-за потенциальных возможностей таргетной терапии. По оценкам различных авторов, примерно от 10  до 15 % случаев рака поджелудочной железы объясняется генетической причиной. Из этих синдромов наследственной предрасположенности наиболее актуальны на сегодня BRCA-мутации. Частота герминальных мутаций в  генах BRCA1/2  и  PALB2  у  пациентов с  аденокарциномой поджелудочной железы составляет около 5–9 %. В  последние годы ингибиторы PARP (PARPi) появились как новый класс таргетной терапии со значительной активностью при раке молочной железы, яичников. Учитывая, что механизм действия PARPингибиторов и препаратов платины различен, они оказывают свое действие на разные пути репарации ДНК, было высказано предположение, что комбинированная терапия может представлять интерес. Авторы сообщили о результатах исследования комбинации велипариба, гемцитабина и цисплатина у пациентов с герминальной мутацией BRCA1/2 и распространенной аденокарциномой поджелудочной железы дикого типа (WT). Последние достижения позволили выявить пациентов с герминальными и соматическими мутациями в генах BRCA1/2 и других. Терапия, направленная на HRD, включая препараты платины и PARP-ингибиторы, может значительно улучшить выживаемость. 

Pancreatic adenocarcinoma has a  5-year overall survival rate of 9 %, with an outlook of becoming the second leading cause of cancer mortality in the USA by 2030. Familial pancreatic cancer and genetic predisposition syndromes have attracted more interest in the perspective of targeted therapy. Various authors estimate genetic causes to account for 10–15 % of pancreatic cancers. The BRCA gene mutations comprise the today’s most relevant genetic predisposition syndrome. The frequency of BRCA1/2 and PALB2 germinal mutations in patients with pancreatic adenocarcinoma constitutes about 5–9 %. Over recent years, PARP inhibitors (PARPi) have composed a new targeted therapy class with a significant effect in breast and ovarian cancers. With the mechanism of action of the PARP inhibitor and platinum drugs targeting different DNA repair pathways, their combination therapy has been suggested as promising. We report studies of a combination treatment with veliparib, gemcitabine and cisplatin in germinal BRCA1/2-mutation patients with advanced wild-type pancreatic adenocarcinoma (WT). Recent advances have identified patients with germinal and somatic mutations in the BRCA1/2 and other genes. HRD-targeted therapy, including platinum and PARP inhibitor drugs, can significantly improve survival. 

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