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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Oncology</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Oncology</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский онкологический журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1028-9984</issn><issn publication-format="electronic">2412-9119</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">115222</article-id><article-id pub-id-type="doi">10.17816/onco115222</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Научные обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Palliative treatment of pancreatic cancer</article-title><trans-title-group xml:lang="ru"><trans-title>Паллиативное консервативное лечение рака поджелудочной железы</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1199-3699</contrib-id><contrib-id contrib-id-type="spin">5795-0530</contrib-id><name-alternatives><name xml:lang="en"><surname>Tseimakh</surname><given-names>Alexander E.</given-names></name><name xml:lang="ru"><surname>Цеймах</surname><given-names>Александр Евгеньевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Med.), Assistant Professor</p></bio><bio xml:lang="ru"><p>к.м.н., доцент</p></bio><email>alevtsei@rambler.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1080-5294</contrib-id><contrib-id contrib-id-type="spin">1161-8387</contrib-id><name-alternatives><name xml:lang="en"><surname>Lazarev</surname><given-names>Alexander  F.</given-names></name><name xml:lang="ru"><surname>Лазарев</surname><given-names>Александр Федорович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Med.), Professor</p></bio><bio xml:lang="ru"><p>д.м.н., профессор</p></bio><email>lazarev@akzs.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5253-4325</contrib-id><contrib-id contrib-id-type="spin">6379-3517</contrib-id><name-alternatives><name xml:lang="en"><surname>Shoykhet</surname><given-names>Yakov  N.</given-names></name><name xml:lang="ru"><surname>Шойхет</surname><given-names>Яков Нахманович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Med.), Professor, Associate Member of Russian Academy of Sciences</p></bio><bio xml:lang="ru"><p>д.м.н., профессор, член-корреспондент РАН</p></bio><email>starok100@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Altai State Medical University</institution></aff><aff><institution xml:lang="ru">Алтайский государственный медицинский университет</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2022-10-14" publication-format="electronic"><day>14</day><month>10</month><year>2022</year></pub-date><volume>27</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>117</fpage><lpage>126</lpage><history><date date-type="received" iso-8601-date="2022-12-07"><day>07</day><month>12</month><year>2022</year></date><date date-type="accepted" iso-8601-date="2023-04-06"><day>06</day><month>04</month><year>2023</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2022, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2022, Эко-Вектор</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2025-10-14"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref></license></permissions><self-uri xlink:href="https://rjonco.com/1028-9984/article/view/115222">https://rjonco.com/1028-9984/article/view/115222</self-uri><abstract xml:lang="en"><p>Pancreatic cancer is one of the most serious problems of modern oncology. In the Russian Federation, pancreatic cancer, along with a fairly small share in the structure of the incidence of malignant neoplasms — 3%, ranks first in annual mortality (68.2%), and is also a nosology with the most unfavorable prognosis among tumors of the gastrointestinal tract. The current standard of first-line therapy is FOLFRINOX (FOLFIRINOX, a combination of 5-fluorouracil (5-FU), leucovorin, irinotecan, and oxaliplatin) or gemcitabine plus albumin-bound nab-paclitaxel.</p> <p>One of the main obstacles to the action of chemotherapeutic drugs is the microenvironment of fibro-solid stromal tumors, which include pancreatic cancer. In order to potentiate the action of chemotherapy and combat the tumor microenvironment, at the present stage, drugs are being considered for influencing the programmed death 1 (PD-1) gene and cytotoxic T-lymphocyte antigen 4 (CTLA-4). Approximately 10–15% of malignant neoplasms of the pancreas are believed to be associated with hereditary mutations, while all neoplasms have somatic mutations in different combinations of driver genes. One of the most common mutations are <italic>BRCA1</italic>/<italic>BRCA2</italic> gene mutations. Poly-ADP-ribose polymerase inhibitors, like cisplatin, have shown promise as a treatment for tumors with <italic>BRCA</italic> mutations.</p> <p>Another subtype of pancreatic cancer is characterized by microsatellite instability. Unlike the above mutations and phenotypes, which affect only a small proportion of patients with pancreatic cancer, mutations in <italic>KRAS</italic> (Kirsten homologous rat sarcoma viral oncogene) are found in 90–95% of cases of pancreatic malignancy and may be a significant factor in pancreatic tumorigenesis. Another frequently mutating gene for a number of malignancies is <italic>ARID1A</italic>, which encodes a tumor suppressor protein, a subunit of the SWI/SNF chromatin remodeling complex.</p> <p>The future of conservative therapy for pancreatic cancer is a complex treatment that includes both chemotherapy and targeted therapy and immunotherapy, the implementation of which is impossible without a deeper study of genetic mutations, molecular mechanisms of invasion and development of pancreatic malignant neoplasms, as well as extensive testing for genetic mutations in the clinical practice of specialized institutions.</p></abstract><trans-abstract xml:lang="ru"><p>Рак поджелудочной железы — одна из наиболее серьёзных проблем современной онкологии. В Российской Федерации он занимает первое место по годичной летальности (68,2%), несмотря на достаточно малую долю в структуре заболеваемости злокачественными новообразованиями (3%), а также является нозологией с самым неблагоприятным прогнозом среди опухолей гастроинтестинального тракта. В настоящее время стандартом терапии первой линии является Фолфиринокс (FOLFIRIONOX — комбинация 5-фторурацила (5-ФУ), лейковорина, иринотекана и оксалиплатина) или комбинация гемцитабина с альбумин-связанным наб-паклитакселом.</p> <p>Одно из главных препятствий для действия химиотерапевтических препаратов — микроокружение фиброзно-солидных стромальных опухолей, к которым относится и рак поджелудочной железы. С целью потенцирования действия химиотерапии и борьбы с микроокружением опухоли на современном этапе рассматриваются препараты для воздействия на рецептор запрограммированной смерти 1 (PD-1) и цитотоксический Т-лимфоцитарный антиген 4 (CTLA-4). Считается, что примерно 10–15% злокачественных новообразований поджелудочной железы связаны с наследственными мутациями, при этом все новообразования имеют соматические мутации в разных комбинациях генов-драйверов. Одними из наиболее частых являются мутации генов <italic>BRCA1</italic>/<italic>BRCA2</italic>. Ингибиторы поли(АДФ-рибоза-)полимеразы, как и цисплатин, показали себя многообещающими для лечения опухолей с мутациями гена <italic>BRCA</italic>.</p> <p>Ещё один подтип рака поджелудочной железы характеризуется микросателлитной нестабильностью. В отличие от вышеизложенных мутаций и фенотипов, которые влияют только на небольшую долю пациентов с раком поджелудочной железы, мутации в <italic>KRAS</italic> (вирусный онкоген саркомы крыс Кирстен гомологический) обнаруживаются в 90–95% случаях злокачественных новообразований поджелудочной железы и могут быть значимым фактором её онкогенеза. Другим часто мутирующим геном для ряда злокачественных новообразований является <italic>ARID1A</italic> — кодирующая белок-супрессор опухолевого роста субъединица комплекса ремоделирования хроматина SWI/SNF.</p> <p>Будущим консервативной терапии рака поджелудочной железы можно считать комплексное лечение, включающее в себя как химиотерапию, так и таргетную и иммунотерапию, внедрение которых невозможно без более глубокого изучения генетических мутаций, молекулярных механизмов инвазии и развития злокачественных новообразований поджелудочной железы, а также широкого тестирования на генетические мутации в клинической практике профильных учреждений.</p></trans-abstract><kwd-group xml:lang="en"><kwd>pancreatic cancer</kwd><kwd>palliative care</kwd><kwd>chemotherapy</kwd><kwd>immunomodulation</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>злокачественные новообразования поджелудочной железы</kwd><kwd>паллиативное лечение</kwd><kwd>химиотерапия</kwd><kwd>иммунотерапия</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Siegel RL, Miller KD, Fuchs HE, Jemal A. 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