oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2025-24-6-160-172oncotomsk-3960Research ArticleОБЗОРЫREVIEWSОртотопические модели в экспериментальной онкологии: обзор литературы. К 150-летию первой успешной серийной трансплантации опухоли у животныхOrthotopic models in cancer research: a literature review. To the 150th anniversary of the first successful serial tumor transplantation in animalshttps://orcid.org/0000-0002-6573-3112МуразовЯ. Г.MurazovIa. G.

Муразов Ярослав Геннадьевич - кандидат биологических наук, руководитель лаборатории онкофармакологии и канцерогенеза.

SPIN-код: 2770-5375.

Researcher ID (WOS): AAY-9767-2021.

Author ID (Scopus): 53863794000.

188663, Ленинградская обл., Всеволожский район, г.п. Кузьмоловский, ул. Заводская, 3, к. 245

Iaroslav G. Murazov - PhD, Head of Laboratory of Oncopharmacology and Carcinogenesis.

Researcher ID (WOS): AAY-9767-2021.

Author ID (Scopus): 53863794000.

245, Zavodskaya St., Kuzmolovskiy t.s., Vsevolozhsk district, Leningrad oblast, 188663

https://orcid.org/0000-0002-0740-9357КовалеваМ. А.KovalevaM. A.

Ковалева Мария Александровна - кандидат биологических наук, руководитель научно-методической группы.

SPIN-код: 3249-0064.

Author ID (Scopus): 36523050900.

188663, Ленинградская обл., Всеволожский район, г.п. Кузьмоловский, ул. Заводская, 3, к. 245

Maria A. Kovaleva - PhD, Head of the scientific and methodological group.

Author ID (Scopus): 36523050900.

245, Zavodskaya St., Kuzmolovskiy t.s., Vsevolozhsk district, Leningrad oblast, 188663

https://orcid.org/0000-0003-1451-7716КрышеньК. Л.KryshenK. L.

Крышень Кирилл Леонидович - кандидат биологических наук, заместитель директора по науке.

SPIN-код: 5650-2840.

188663, Ленинградская обл., Всеволожский район, г.п. Кузьмоловский, ул. Заводская, 3, к. 245

Kirill L. Kryshen - PhD, Deputy Director for Science.

245, Zavodskaya St., Kuzmolovskiy t.s., Vsevolozhsk district, Leningrad oblast, 188663

https://orcid.org/0000-0003-3176-6386МакароваМ. Н.MakarovaM. N.

Макарова Марина Николаевна - доктор медицинских наук, директор.

SPIN-код: 2479-7871.

Author ID (Scopus): 22951358800.

188663, Ленинградская обл., Всеволожский район, г.п. Кузьмоловский, ул. Заводская, 3, к. 245

Marina N. Makarova - MD, DSc, Director.

Author ID (Scopus): 22951358800.

245, Zavodskaya St., Kuzmolovskiy t.s., Vsevolozhsk district, Leningrad oblast, 188663

https://orcid.org/0000-0002-2447-7888МакаровВ. Г.MakarovV. G.

Макаров Валерий Геннадьевич - доктор медицинских наук, профессор, научный руководитель.

SPIN-код: 5279-6329.

Researcher ID (WOS): F-8746-2016.

Author ID (Scopus): 7401690256.

188663, Ленинградская обл., Всеволожский район, г.п. Кузьмоловский, ул. Заводская, 3, к. 245

Valery G. Makarov - MD, DSc, Professor, Scientific Supervisor.

Researcher ID (WOS): F-8746-2016.

Author ID (Scopus): 7401690256.

245, Zavodskaya St., Kuzmolovskiy t.s., Vsevolozhsk district, Leningrad oblast, 188663

Акционерное общество «Научно-производственное объединение «ДОМ ФАРМАЦИИ»РоссияResearch and manufacturing company “Home оf Pharmacy”Russian Federation202513012026246160172Copyright © Муразов Я.Г., Ковалева М.А., Крышень К.Л., Макарова М.Н., Макаров В.Г., 20262026Муразов Я.Г., Ковалева М.А., Крышень К.Л., Макарова М.Н., Макаров В.Г.Murazov I.G., Kovaleva M.A., Kryshen K.L., Makarova M.N., Makarov V.G.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/3960Актуальность

Актуальность. Трансплантируемые модели с использованием аллографтов и ксенографтов опухолей человека остаются незаменимым инструментом в экспериментальной онкологии для изучения механизмов канцерогенеза и оценки противоопухолевой активности перспективных средств лечения злокачественных новообразований.

Цель исследования – провести традиционный анализ научной литературы, посвященной возможностям метода ортотопической трансплантации у лабораторных животных с использованием различных источников получения опухолевого материала; описать основные преимущества и ограничения ортотопических моделей; представить практические рекомендации, которые помогут исследователям в рутинной практике при работе с ортотопическими трансплантируемыми моделями.

Материал и методы

Материал и методы. Поиск публикаций выполняли в базах данных PubMed и Google Scholar. В обзор включали релевантные публикации, доступные для поиска на 30 апреля 2025 г.

Результаты

Результаты. Показано, что по сравнению с трансплантацией суспензий опухолевых клеток, культивированных in vitro, трансплантация фрагментов со́лидных опухолей обеспечивает сохранение клональной гетерогенности опухоли, компонентов ее микроокружения и внеклеточного матрикса, которые поддерживают энграфтмент и рост опухоли. В сравнении с подкожной перевивкой ортотопические модели более точно воспроизводят сложное взаимодействие в системе «опухоль-организм хозяина» и патологические особенности злокачественных новообразований человека, включая метастатическую болезнь. Поскольку ортотопические опухоли находятся в естественном микроокружении, доклиническая оценка ответа таких опухолей в дальнейшем лучше транслируется в ранние фазы клинического изучения.

Заключение

Заключение. Включение ортотопических моделей в программы неклинических фармакодинамических исследований in vivo дает возможность получить более полное представление о противоопухолевой активности проводимого экспериментального лечения, а также повышает прогностическую ценность и надежность доклинических результатов.

Background

Background. Transplantation models, including allografts and xenografts are crucial in oncology research because they help study the mechanisms of carcinogenesis and assess the activity of promising antitumor agents.

Objectives

Objectives: 1) to conduct a traditional analysis of scientific literature devoted to orthotopic transplantation in laboratory animals using various sources of tumor material, 2) to describe the main advantages and limitations of orthotopic models, 3) to provide practical recommendations for researchers dealing with orthotopic transplantation models.

Material and Methods

Material and Methods. A search was conducted in PubMed and Google Scholar bibliographic databases. The review included relevant publications available for search until April 30, 2025.

Results

Results. Compared to transplantation of tumor cell suspensions cultured in vitro, transplantation of solid tumor fragments ensures preservation of the clonal heterogeneity of the tumor, components of its microenvironment and extracellular matrix, which support engraftment and tumor growth. Compared to subcutaneous transplantation, orthotopic models offer a more realistic depiction of the complex interactions in the tumor-host system and the pathological characteristics of human cancers, particularly those involving metastasis. Because orthotopic tumors exist within their natural environment, the evaluation of their response during preclinical research is more likely to be translatable in the initial phases of clinical trials.

Conclusion

Conclusion. Incorporating orthotopic models into non-clinical in vivo pharmacodynamic research programs improve the predicitve value and dependability of preclinical results and offer a chance to gain a more thorough understanding of the antitumor activity of the experimental treatment.

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