tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2018-8-4-13-25tumors-586Research ArticleСтатьиМолекулярные механизмы резистентности к терапии моноклональными антителами у больных плоскоклеточным раком языка и слизистой дна полости ртаMolecular mechanisms of resistance to monoclonal antibodies therapy patients with squamous cell carcinoma of the tongue and mucosa of the oral cavityВладимироваЛ. Ю.VladimirovaL. Yu.

д. м. н., проф., руководитель отдела лекарственного лечения опухолей, руководитель отделения противоопухолевой лекарственной терапии № 1

MD, DSc Med, Professor, Head of the Department of Medical Treatment, Head of the Tumor Drug Therapy Department No. 1

vlu@aaanet.ruЛьяноваА. А.LyanovaA. A.

врач-онколог отделения противоопухолевой лекарственной терапии № 1,

MD, oncologist, Tumor Drug Therapy Department No. 1

blackswan-11@mail.ruФранциянцЕ. М.FrantsiyantsE. M.

д. м. н., проф., руководитель лаборатории иммунофенотипирования опухолей

MD, DSc Med, Professor, Head of the Laboratory of Immunophenotyping of Tumors

super.gormon@yandex.ruКутилинД. С.KutilinD. S.

к. б. н., с. н. с. лаборатории молекулярной онкологии

MD, PhD Biol, Senior Researcher, Laboratory of Molecular Oncology

fired2007@rambler.ruЕнгибарянМ. А.EngibaryanM. A.

к. м. н., зав. отделением опухолей головы и шеи

MD, PhD Med, Head of the Department of Head and Neck Tumors

rnioi@list.ruФГБУ «Ростовский научно-исследовательский онкологический институт» Министерства здравоохранения РФ, Ростов-на-ДонуРоссияRostov Research Institute of OncologyRussian Federation201822012019841325Copyright © Владимирова Л.Ю., Льянова А.А., Франциянц Е.М., Кутилин Д.С., Енгибарян М.А., 20192019Владимирова Л.Ю., Льянова А.А., Франциянц Е.М., Кутилин Д.С., Енгибарян М.А.Vladimirova L.Y., Lyanova A.A., Frantsiyants E.M., Kutilin D.S., Engibaryan 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.malignanttumors.org/jour/article/view/586

В обзоре проведен анализ современных данных о молекулярных механизмах резистентности к терапии моноклональными антителами у больных плоскоклеточным раком языка и слизистой дна полости рта. Подробно описаны механизмы резистентности к моноклональным анти-ERBB-антителам и анти-PD1‑антителам и пути ее преодоления. Проведенный анализ позволил выделить ряд факторов, которые необходимо учитывать при назначении терапии моноклональными антителами: активацию альтернативных рецептрорных тирозин киназ; повышение экспрессии генов лигандов рецепторов; мутации в эффекторах и самих рецептрорных тирозин-киназах; нарушение образования функциональных димеров рецепторов; изменения в белках и кодирующих их генах, ответственных за регуляцию каскадов апоптоза, митоза, эпителиально-мезенхимального перехода; секрецию противовоспалительных цитокинов и иммуносупрессорных метаболитов.

The review analyzes current data on the molecular mechanisms of resistance to monoclonal antibodies in patients withsquamous cell carcinoma of the tongue and mucosa of the oral cavity. The mechanisms of resistance to monoclonal anti-ERBBand anti-PD1 antibodies and ways to overcome it are described in detail. The analysis made it possible to identify a number of factorsthat should be taken into account when assigning therapy with monoclonal antibodies: activation of alternative receptor tyrosinekinases, increased expression of receptor ligand genes, mutations in effectors and the receptor tyrosine kinases themselves, disruptionof the formation of functional receptor dimers, changes in proteins and coding for them genes responsible for the regulation ofcascades of apoptosis, mitosis, epithelial-mesenchymal transition, secretion of anti-inflammatory cytokines and immunosuppressivemetabolites.

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