medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-534medsovet-8783Research ArticleТАРГЕТНАЯ ТЕРАПИЯTARGET THERAPY OF TUMORSТранслокации NTRK: от общего к частномуNTRK translocation: from general to specifichttps://orcid.org/0000-0001-7604-6396СоловьеваМ. В.SolovevaM. V.

Соловьева Мария Владимировна, ординатор отделения лекарственных методов лечения (химиотерапевтическое) №17

115478, Москва, Каширское шоссе, д. 24

Mariia V. Soloveva, Resident of the Oncological Department of Medical Treatment Methods (Chemotherapeutic) No. 17

24, Kashirskoye Shosse, Moscow, 115478

solo_mariyka@mail.ruhttps://orcid.org/0000-0003-4469-502XЛактионовК. К.LaktionovK. K.

Лактионов Константин Константинович, д.м.н., профессор кафедры онкологии и лучевой терапии лечебного факультета; заведующий онкологическим отделением лекарственных методов лечения (химиотерапевтическое) №17

117997, Москва, ул. Островитянова, д. 1

115478, Москва, Каширское шоссе, д. 24 

Konstantin K. Laktionov, Dr. Sci. (Med.), Professor of the Department of Oncology and Radiation Therapy of the Faculty of Medicine; Head of the Oncological Department of Medical Treatment Methods (Chemotherapeutic) No. 17

1, Ostrovityanov St., Moscow, 117997

24, Kashirskoye Shosse, Moscow, 115478

lkoskos@mail.ruhttps://orcid.org/0000-0002-7817-8429СаранцеваК. А.SarantsevaK. A.

Саранцева Ксения Андреевна, к.м.н., врач-онколог, научный сотрудник отделения противоопухолевой лекарственной терапии №3 отдела лекарственных методов лечения; доцент кафедры онкологии и лучевой терапии лечебного факультета

115478, Москва, Каширское шоссе, д. 24

117997, Москва, ул. Островитянова, д. 1

Ksenia A. Sarantseva, Cand. Sci. (Med.), Oncologist, Researcher of the Chemotherapy Department No. 3; Assistant Professor of the Department of Oncology and Radiation Therapy, Faculty of Medicine

24, Kashirskoye Shosse, Moscow, 115478

1, Ostrovityanov St., Moscow, 117997

sarantsevaka@gmail.comhttps://orcid.org/0000-0002-3848-865XГордиевМ. Г.GordievM. G.

Гордиев Марат Гордиевич, к.м.н., врач КДЛ

115580, Москва, Ореховый бульвар, д. 49, к. 1

Marat G. Gordiev, Cand. Sci. (Med.)

49, Bldg. 1, Orekhovy Boulevard, Moscow, 115580

marat7925@gmail.comНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian FederationНациональный медицинский исследовательский центр онкологии имени Н.Н. Блохина; Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияBlokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical UniversityRussian FederationЦентр лабораторных исследованийРоссияCenter for Laboratory ResearchRussian Federation2024221220240215261Copyright © Соловьева М.В., Лактионов К.К., Саранцева К.А., Гордиев М.Г., 20242024Соловьева М.В., Лактионов К.К., Саранцева К.А., Гордиев М.Г.Soloveva M.V., Laktionov K.K., Sarantseva K.A., Gordiev M.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.med-sovet.pro/jour/article/view/8783

Молекулярно-генетический профиль рака легкого весьма разнообразен, что затрудняет формирование единого портрета пациента и требует вовлечение определенных генетических тестирований в диагностику. Существуют основные механизмы активации онкогенов, включающие в себя точечные мутации, изменения числа копий (амплификации) и слияния (fusion), которые встречаются при немелкоклеточном раке легкого (НМРЛ). Современная молекулярно-направленная терапия у пациентов с НМРЛ увеличивает длительность контроля над заболеванием, а в некоторых случаях переводит некогда смертельное заболевание в хроническое. На данный момент в стандартный объем тестирования входит определение мутаций в гене EGFR 18–21 экзоны, транслокаций ALK, транслокаций ROS1 и мутаций BRAF V600E. Однако встречаются менее распространенные нарушения, такие как транслокации RET, NTRK. Использование секвенирования следующего поколения (NGS) позволяет выявить более редкие генетические нарушения. Транслокации, слияния генов NTRK считаются онкогенными факторами различных солидных опухолей как у взрослых, так и у детей. Распространенность нарушений в гене NTRK варьируется в зависимости от типа опухоли. Однако при раке легкого такой тип генетических нарушений встречается редко, с общей распространенностью менее 3%, но, как правило, частота встречаемости составляет менее 1%. На данный момент 3 препарата уже находятся в зарубежных клинических рекомендациях как возможные опции лечения в случае транслокации NTRK, доказав свою эффективность. Несколько препаратов находятся на различных этапах клинических исследований. В обзоре мы осветим имеющиеся данные для лучшего понимания профиля пациента с NTRK, а также представим клинический случай.

The molecular-genetic profile of lung cancer is highly diverse, complicating the formation of a unified patient portrait and necessitating the incorporation of specific genetic testing into diagnosis. There are key mechanisms for the activation of oncogenes, including point mutations, copy number changes (amplifications), and fusions, which are observed in non-small cell lung cancer (NSCLC). Modern molecular-targeted therapy for patients with NSCLC increases the duration of disease control and, in some cases, can transform a once-fatal disease into a chronic condition. Currently, the standard testing panel includes the identification of mutations in the EGFR gene (exons 18–21), ALK translocations, ROS1 translocations, and BRAF V600E mutations. However, less common alterations such as RET and NTRK translocations also occur. The use of next-generation sequencing (NGS) allows for the identification of rarer genetic alterations. NTRK gene fusions are considered oncogenic factors for various solid tumors in both adults and children. The prevalence of NTRK gene alterations varies by tumor type. However, in lung cancer, this type of genetic alteration is rare, with an overall prevalence of less than 3%, and typically the occurrence rate is less than 1%. Currently, three drugs have been included in international clinical guidelines as potential treatment options for NTRK translocations, demonstrating their effectiveness. Several other drugs are at various stages of clinical trials. In this review, we will highlight the existing data for a better understanding of the patient profile with NTRK and present a clinical case.

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