oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2025-24-3-149-161oncotomsk-3672Research ArticleОБЗОРЫREVIEWSСовременные представления о молекулярных механизмах развития и генетической предрасположенности к раку поджелудочной железыContemporary insights into the molecular mechanisms of development and genetic susceptibility to pancreatic cancerhttps://orcid.org/0009-0008-2224-7414СперидоноваА. Д.SperidonovaA. D.

Сперидонова Ассоль Дмитриевна - младший научный сотрудник, Институт биохимии и генетики.

450054, Уфа, проспект Октября, 71

Assol D. Speridonova - Junior Researcher, Institute of Biochemistry and Genetics – Subdivision.

71, Prospect Oktyabrya St., Ufa, 450054

https://orcid.org/0000-0001-6975-5151ЗариповаА. Р.ZaripovaA. R.

Зарипова Алия Рамилевна - кандидат биологических наук, научный сотрудник, Институт биохимии и генетики. SPIN-код: 8557-4288. Researcher ID (WOS): AAA-18932022. Author ID (Scopus): 57217061659.

450054, Уфа, проспект Октября, 71

Aliya R. Zaripova – PhD, Researcher, Institute of Biochemistry and Genetics – Subdivision. Researcher ID (WOS): AAA-1893-2022. Author ID (Scopus): 57217061659.

71, Prospect Oktyabrya St., Ufa, 450054

https://orcid.org/0000-0001-9499-5632ГилязоваИ. Р.GilyazovaI. R.

Гилязова Ирина Ришатовна - кандидат биологических наук, доцент, старший научный сотрудник, Институт биохимии и генетики Уфимского исследовательского центра РАН; доцент кафедры медицинской генетики и фунда ментальной медицины, старший научный сотрудник Института урологии и клинической онкологии, Башкирский государственный медицинский университет. SPIN-код: 5799-4821. Researcher ID (WOS): E-5798-2014. Author ID (Scopus): 15848327000.

450054, Уфа, проспект Октября, 71; 450008, Уфа, ул. Ленина, 3

Irina R. Gilyazova - PhD, Associate Professor, Senior Researcher, Institute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Center of the Russian Academy of Sciences; Associate Professor, Department of Medical Genetics and Fundamental Medicine, Senior Researcher, Institute of Urology and Clinical Oncology, Bashkir SMU. Author ID (Scopus): 15848327000.

71, Prospect Oktyabrya St., Ufa, 450054; 3, Lenina St., Ufa, 450008

https://orcid.org/0000-0002-0584-3969БермишеваМ. А.BermishevaM. A.

Бермишева Марина Алексеевна - доктор биологических наук, ведущий научный сотрудник, Институт биохимии и генетики Уфимского исследовательского центра РАН; доцент кафедры биологии, Башкирский государственный медицинский университет. SPIN-код: 6220-2619. Rese450054, Уфа, проспект Октября, 71; 450008, Уфа, ул. Ленина, 3

Marina A. Bermisheva - DSc, Leading Researcher, Institute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Center of the Russian Academy of Sciences; Associate Professor, Department of Biology, Bashkir SMU. Researcher ID (WOS): J-6305-2018. Author ID (Scopus): 8775533800.

71, Prospect Oktyabrya St., Ufa, 450054; 3, Lenina St., Ufa, 450008

marina_berm@mail.ruИнститут биохимии и генетики Уфимского исследовательского центра Российской академии наук РоссияРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Center of the Russian Academy of SciencesRussian FederationИнститут биохимии и генетики Уфимского исследовательского центра Российской академии наук Россия; Башкирский государственный медицинский университетРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Center of the Russian Academy of Sciences; Bashkir State Medical UniversityRussian Federation202504082025243149161Copyright © Сперидонова А.Д., Зарипова А.Р., Гилязова И.Р., Бермишева М.А., 20252025Сперидонова А.Д., Зарипова А.Р., Гилязова И.Р., Бермишева М.А.Speridonova A.D., Zaripova A.R., Gilyazova I.R., Bermisheva M.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.siboncoj.ru/jour/article/view/3672

Рак поджелудочной железы (РПЖ) – заболевание, характеризующееся злокачественными новообразованиями с агрессивным течением и высоким уровнем летальности. Протоковая аденокарцинома составляет около 90 % новообразований поджелудочной железы (ПЖ) и в большинстве случаев детектируется на поздней стадии. В настоящее время эффективного скрининга не существует.

Цель исследования – обобщение имеющихся данных в научной и медицинской литературе о генах предрасположенности и молекулярных механизмах РПЖ.

Материал и методы

Материал и методы. Поиск соответствующих источников производился в системах PubMed (NCBI), Elibrary, GoogleScholar, включались публикации с января 2000 г. по декабрь 2024 г. Из 959 проанализированных работ 60 использованы для написания обзора, 27 из которых опубликованы за последние пять лет.

Результаты

Результаты. До 10 % пациентов с аденокарциномой ПЖ являются носителями герминальных патогенных вариантов, обусловливающих повышенный риск развития РПЖ. Эти варианты встречаются, главным образом, в генах репарации повреждений ДНК. Сложные многоступенчатые генетические изменения происходят в опухолевых клетках, их накопление приводит к инициации ряда онкогенов, которые способствуют развитию РПЖ. Исследования в области молекулярной генетики позволяют выделить группы пациентов с определенными генетическими нарушениями, которым необходимо назначение таргетных препаратов.

Заключение

Заключение. Представлен обзор современных представлений о генетической предрасположенности к РПЖ. Описана функциональная/клиническая значимость белков, вовлеченных в патогенез заболевания. Рассмотрены генетические нарушения, характерные для РПЖ.

Background

Background. Pancreatic cancer (PC) is an aggressive malignancy with a high mortality rate. Pancreatic ductal adenocarcinoma constitutes approximately 90 % of pancreatic cancers, and is frequently diagnosed at an advanced stage. The disease is distinguished by the presence of tumor micrometastasis prior to the onset of clinical symptoms, as well as rapid progression. There are currently no effective screening methods for the disease.

Aim of the study

Aim of the study: analysis of available literature data about susceptibility genes and molecular mechanisms of PC.

Material and methods

Material and methods. The search for relevant sources was performed in the PubMed (NCBI), Elibrary, GoogleScholar, publications from January 2000 to December 2024 were included. Of the 959 papers analyzed, 60 were used to write the review, 27 of which were published in the last five years.

Results

Results. Approximately 10 % of pancreatic adenocarcinoma patients are carriers of germinal pathogenic variants that cause an increased risk of PC. These variants predominantly occur in DNA damage repair genes. Tumor cells undergo complex multistep genetic alterations, and the accumulation of these changes facilitates the activation of various oncogenes that contribute to the progression of PC. Research in the field of molecular genetics makes it possible to identify groups of patients with certain genetic alterations who need to be prescribed targeted drugs.

Conclusion

Conclusion. This article provides an overview of current understanding of the genetic predisposition to PC. The functional/clinical significance of proteins involved in the pathogenesis of the disease was described. Genetic alterations of PC were discussed.

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