Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press30010.17650/2313-805X-2020-7-4-20-28REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИAntitumor proteinkinase inhibitor imatinib may be regarded as a potential correcting agent for COVID-19 associated pulmonary fibrosisПротивоопухолевый ингибитор протеинтирозинкиназ иматиниб как потенциальный корректор пневмофиброза COVID-19https://orcid.org/0000-0002-7659-6045MikhaylovaI. N.МихайловаИ. Н.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

Ирина Николаевна Михайлова

115478 Москва, Каширское шоссе, 24 

irmikhaylova@gmail.comhttps://orcid.org/0000-0002-3878-3958TreshalinaN. M.ТрещалинаЕ. М.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-9374-3158ShubinaI. Zh.ШубинаИ. Ж.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

ManinaI. V.МанинаИ. В.
Russian Federation

Build. 1, 20 Malaya Bronnaya St., Moscow 123104

123104 Москва, Малая Бронная ул., 20, стр. 1

https://orcid.org/0000-0002-0132-167XKiselevskyM. V.КиселевскийМ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-7365-0352LukashevA. N.ЛукашевА. Н.
Russian Federation

Build. 1, 20 Malaya Pirogovskaya St., Moscow 119435

119435 Москва, Малая Пироговская ул., 20, стр. 1

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииInstitute of Allergology and Clinical ImmunologyООО «Институт аллергологии и клинической иммунологии»Research Institute of Medical Parasitology, Tropical and Vector-borne Diseases named after E. I. Marcinovsky, I. M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of RussiaНаучно-исследовательский институт медицинской паразитологии и тропической медицины им. Е. И. Марциновского ФГАОУ ВО Первый Московский государственный медицинский университет им. И. М. Сеченова (Сеченовский Университет) Минздрава России151220207420281201202112012021Copyright ©; 2020, Mikhaylova I.N., Treshalina N.M., Shubina I.Z., Manina I.V., Kiselevsky M.V., Lukashev A.N.Copyright ©; 2020, Михайлова И.Н., Трещалина Е.М., Шубина И.Ж., Манина И.В., Киселевский М.В., Лукашев А.Н.2020Mikhaylova I.N., Treshalina N.M., Shubina I.Z., Manina I.V., Kiselevsky M.V., Lukashev A.N.Михайлова И.Н., Трещалина Е.М., Шубина И.Ж., Манина И.В., Киселевский М.В., Лукашев А.Н.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/300

Imatinib mesilate is a well-known antitumor target inhibitor of protein tyrosine kinase, which is effective in different cancer types expressing Bcr / Abl and, in particular, in hemoblastosis. A higher interest to imatinib during the COVID-19 epidemic is explained by the fact that cancer patients are one of the COVID-19 risk groups. Moreover, imatinib target mechanism of action, which is effective in cancer, can have a high potential against the most severe COVID-19 complication such as the disease associated pulmonary fibrosis. COVID-19 associated interstitial pulmonary fibrosis develops as an autoimmune process caused by systemic inflammation with atypical (idiopathic) pneumonia resulting from acute respiratory distress syndrome with the tyrosine kinase mechanism of signaling pathway activation and cellular response. Experi-mental and clinical results showing antifibrotic and dose-related antithrombotic imatinib effect demonstrate perspective use of this antitumor agent to correct COVID-19 associated pneumonia causing a high death rate of patients with COVID-19.The review presents literature data of 2001–2020 discussing pathologic genetic and clinical characteristics of the fibrosis which exacerbates COVID-19 pneumonia in adults. The sequence of the disease processes demonstrates that disease progression with the decreasing oxygen saturation in the peripheral blood intensifies local thrombosis in the lungs. As a result, hypoxia is developing, which is difficult to control and can cause lethal outcome in severe cases. Yet, the conventional antifibrotic and thrombolytic agents can only partially control the process of pneumofibrosis including that of cancer patients. The approximate antifibrotic dose of imatinib 400 mg / day is therapeutic for oncopatho-logy. The antitumor drug registered in many countries and well described side effects and contraindications needs no long-term registration studies for a new indication, therefore, it may be easily prepared for clinical testing.

Иматиниб мезилат – известный противоопухолевый таргетный ингибитор протеиновых тирозинкиназ, эффективный при раз-личной онкологической патологии с экспрессией Bcr / Abl, особенно при гемобластозах. На фоне пандемии коронавируса COVID-19 интерес к иматинибу возрос в связи с тем, что онкологические пациенты относятся к одной из групп риска заболевания COVID-19. Более того, определяющий применение иматиниба при онкологических заболеваниях таргетный механизм дейст-вия может быть перспективен для коррекции наиболее опасного осложнения – COVID-19-ассоциированного пневмофиброза. COVID-19-ассоциированный интерстициальный пневмофиброз возникает аутоиммунно вследствие системного воспаления с развитием атипичной (идиопатической) пневмонии под действием острого респираторного дистресс-синдрома с тирозин-киназным механизмом активации сигнальных путей и клеточного ответа. Экспериментальные и клинические данные, выявив-шие антифибротическое и дозозависимое антитромботическое действие иматиниба, свидетельствуют о целесообразности применения этого противоопухолевого препарата для коррекции COVID-19-ассоциированной пневмонии – причины высокой смертности пациентов с COVID-19.В обзоре приведены данные литературы 2001–2020 гг., посвященные патогенетическим и клиническим особенностям развития пневмофиброза, проанализированы данные об особенностях течения пневмонии COVID-19 у взрослых. Приведенная последователь-ность событий показывает, что прогрессирование процесса со снижением сатурации кислорода в периферической крови усили-вает локальное тромбообразование в легких. В результате возникает плохо управляемая гипоксия, которая в тяжелых случаях является причиной летального исхода. Воздействие на процесс развития пневмофиброза с помощью известных антифибротиче-ских и тромболитических препаратов позволяет лишь частично контролировать процесс, в том числе у онкологических пациен-тов. Ориентировочная антифибротическая доза иматиниба 400 мг / сут считается терапевтической для онкологической пато-логии. Зарегистрированный во многих странах противоопухолевый препарат не требует длительных регистрационных исследований по новому показанию, а известные побочные эффекты и противопоказания к применению позволяют быстро под-готовить его клиническую апробацию.

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