cancerspЮжно-Российский онкологический журнал/ South Russian Journal of CancerSouth Russian Journal of Cancer2686-9039АНО "Перспективы онкологии"10.37748/2686-9039-2022-3-2-5cancersp-170Research ArticleОБЗОРЫREVIEWSСовременное лечение ALK- позитивного немелкоклеточного рака легкогоModern treatment of ALK-positive non-small cell lung cancerhttps://orcid.org/0000-0003-0640-2994ХарагезовД. А.KharagezovD. A.

Харагезов Дмитрий Акимович – кандидат медицинских наук, хирург, заведующий отделением торакальной онкологии

Ростов-на-Дону

SPIN: 5120-0561,

AuthorID: 733789,

ResearcherID: AAZ-3638-2021,

Scopus Author ID: 56626499300

Dmitriy A. Kharagezov – Cand. Sci. (Med.), surgeon, head of the department of thoracic oncology

Rostov-on-Don

SPIN: 5120-0561,

AuthorID: 733789,

ResearcherID: AAZ-3638- 2021,

Scopus Author ID: 56626499300

dmitr8@mail.ruhttps://orcid.org/0000-0002-6655-7632ЛазутинЮ. Н.LazutinYu. N.

Лазутин Юрий Николаевич – кандидат медицинских наук, доцент, ведущий научный сотрудник отдела торакоабдоминальной онкологии

Ростов-на-Дону

SPIN: 5098-7887,

AuthorID: 364457

Yuriy N. Lazutin – Cand. Sci. (Med.), associate professor, leading researcher of the department of thoracoabdominal oncology

Rostov-on-Don

SPIN: 5098-7887,

AuthorID: 364457

lazutin.jurij@yandex.ruhttps://orcid.org/0000-0002-0328-9714МирзоянЭ. А.MirzoyanE. A.

Мирзоян Эллада Арменовна – аспирант

344037, г. Ростов-на-Дону, ул. 14-я линия, д. 63

SPIN: 2506-8605,

AuthorID: 1002948

ResearcherID: AAZ-2780-2021

Scopus Author ID: 57221118516

Ellada A. Mirzoyan – PhD student

63 14 line str., Rostov-on-Don 344037

SPIN: 2506-8605,

AuthorID: 1002948,

ResearcherID: AAZ-2780-2021,

Scopus Author ID: 57221118516

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0002-2589-7606МилакинА. Г.MilakinA. G.

Милакин Антон Григорьевич – онколог отделения торакальной онкологии

Ростов-на-Дону

SPIN: 7737-4737,

AuthorID: 794734

Anton G. Milakin – MD, oncologist of the department of thoracic oncology

Rostov-on-Don

SPIN: 7737-4737,

AuthorID: 794734

amilakin@yandex.ruhttps://orcid.org/0000-0003-4513-7548СтатешныйО. Н.StateshnyO. N.

Статешный Олег Николаевич – онколог отделения торакальной онкологии

Ростов-на-Дону

SPIN: 9917-1975,

AuthorID: 1067071

Oleg N. Stateshny – MD, oncologist of the department of thoracic oncology

Rostov-on-Don

SPIN: 9917-1975,

AuthorID: 1067071

stateshny@rambler.ruhttps://orcid.org/0000-0003-2572-1624ЛейманИ. А.LeymanI. A.

Лейман Игорь Александрович – кандидат медицинских наук, врач-онколог отделения торакальной хирургии

Ростов-на-Дону

SPIN: 2551-0999,

AuthorID: 735699

Igor A. Leyman – Cand. Sci. (Med.), MD, oncologist of the department of thoracic surgery

Rostov-on-Don

SPIN: 2551-0999,

AuthorID: 735699

toraxrnioi@yandex.ruhttps://orcid.org/0000-0002-6655-7632ГаппоеваМ. А.GappoevaM. A.

Гаппоева Мадина Асланбековна – онколог клинико-диагностического отделения

Ростов-на-Дону

SPIN-код: 2551-0999

Madina A. Gappoeva – oncologist of the clinical and diagnostic department

Rostov-on-Don

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0002-9603-1607ВитковскаяВ. Н.VitkovskayaV. N.

Витковская Виктория Николаевна – онколог клинико-диагностического отделения

Ростов-на-Дону

 

Viktoriia N. Vitkovskaya – oncologist of the clinical and diagnostic department

Rostov-on-Don

VickyS8@mail.ruhttps://orcid.org/0000-0002-5351-3251ИозефиК. Д.IozefiK. D.

Иозефи Кристиан Дмитриевич – аспирант

Ростов-на-Дону

SPIN: 1232-3097,

AuthorID: 1122592,

ResearcherID: AAZ-3632-2021

Kristian D. Iozefi – PhD student

Rostov-on-Don

SPIN: 1232-3097,

AuthorID: 1122592,

ResearcherID: AAZ-3632-2021

K.iozeffi@gmail.comНМИЦ онкологииРоссияNational Medical Research Centre for OncologyRussian Federation202228042022324151Copyright © Харагезов Д.А., Лазутин Ю.Н., Мирзоян Э.А., Милакин А.Г., Статешный О.Н., Лейман И.А., Гаппоева М.А., Витковская В.Н., Иозефи К.Д., 20222022Харагезов Д.А., Лазутин Ю.Н., Мирзоян Э.А., Милакин А.Г., Статешный О.Н., Лейман И.А., Гаппоева М.А., Витковская В.Н., Иозефи К.Д.Kharagezov D.A., Lazutin Y.N., Mirzoyan E.A., Milakin A.G., Stateshny O.N., Leyman I.A., Gappoeva M.A., Vitkovskaya V.N., Iozefi K.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cancersp.com/jour/article/view/170

Рак легкого (РЛ) занимает первое место в структуре общей онкологической заболеваемости мужского населения. Ежегодно в мире РЛ диагностируется более чем у 1,8 миллиона человек и остается основной причиной смертности от злокачественных новообразований как в развивающихся, так и в развитых странах, а 5 летняя выживаемость, достигающая 19 % вызывает разочарование. Подобные неудовлетворительные исходы объясняются многими факторами, включая диагностику РЛ на поздней стадии, когда излечение остается редким при доступных на сегодняшний день методах лечения. Немелкоклеточный рак легкого (НМРЛ) с хромосомной перестройкой киназы анапластической лимфомы (ALK) чувствителен к таргетной терапии ингибиторами тирозинкиназы (ТКИ). Опухолевые клетки, содержащие слияние ALK, чувствительны к ингибиторам TKИ – таргетным препаратам, которые существенно улучшили результаты лечения больных ALK-позитивным НМРЛ, половина из которых выживают более 6,8 года после установления диагноза. Количество пациентов с ALK-позитивным НМРЛ варьируется, так ALK реаранжировки обнаруживаются примерно в 3–7 % аденокарцином легкого, что составляет до 60 000 новых случаев заболевания ежегодно во всем мире. ALK-позитивный НМРЛ наблюдается почти исключительно при аденокарциномах, ассоциированных с лицами более молодого возраста, мужского пола и никогда не курившими или курившими мало. Больным ALK-позитивным НМРЛ I–III стадии показано лечение аналогичное пациентам с НМРЛ дикого типа, включая хирургическое вмешательство, лучевую терапию, химиотерапию или мультимодальное лечение в зависимости от стадии опухолевого процесса. В последние десятилетие разработано несколько ALK ТКИ и среди них алектиниб, который в настоящее время является препаратом выбора первой линии терапии больных, не получавших лечения. Изучение механизмов резистентности привело к разработке ингибиторов ALK следующего поколения, которые лучше проникают в центральную нервную систему, активно воздействуя на метастазы в головном мозге. Данный обзор освещает современное состояние и перспективы развития терапии ALK-позитивного НМРЛ.

Lung cancer (LC) takes the first place in the structure of overall oncology in males. More than 1.8 million of new cases of lung cancer (LC) are registered each year worldwide. LC is the leading cause of cancer death in both developing and developed countries, and the 5 years survival rate is as low as 19 %. Many factors explain such unsatisfactory outcomes, including the LC diagnosis at an advanced stage, when the currently available treatments can rarely provide cure. Non-small cell lung cancer (NSCLC) with chromosomal rearrangement of anaplastic lymphoma kinase (ALK) is sensitive to targeted therapy with tyrosine kinase inhibitors (TKIs). Tumor cells containing ALK fusion are sensitive to TKIs – targeted drugs that have significantly improved the results of treatment of patients with ALK-positive NSCLC, half of whom survive more than 6.8 years after diagnosis. The number of patients with ALK-positive NSCLC varies, so ALK rearrangements are detected in about 3–7 % of lung adenocarcinomas, which accounts for up to 60.000 new cases of the disease annually worldwide. ALK-positive NSCLC is observed almost exclusively in adenocarcinomas associated with persons of younger age, male and never smoked or smoked a little. Patients with ALK-positive stage I–III NSCLC are shown treatment similar to patients with wild-type NSCLC, including surgery, radiation therapy, chemotherapy or multimodal treatment, depending on the stage of the tumor process. Numerous ALK TKIs have been developed in recent years, including alectinib, which is the current preferred first-line agent for patients who haven’t received therapy. The study of the mechanisms of resistance has led to the development of next-generation ALK inhibitors that better penetrate the central nervous system, actively affecting brain metastases. This review highlights the current state and prospects for the development of ALK-positive NSCLC therapy.

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